International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 73

WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 61 International Nonproprietary Names for Pharmaceutical Substances (INN) RECOMMENDED International Nonproprietary Names: List 73 Notice is hereby given that, in accordance with paragraph 7 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances [Off. Rec. Wld Health Org., 1955, 60, 3 (Resolution EB15.R7); 1969, 173, 10 (Resolution EB43.R9); Resolution EB115.R4 (EB115/2005/REC/1)], the following names are selected as Recommended International Nonproprietary Names. The inclusion of a name in the lists of Recommended International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (1–109) and Recommended (1–70) International Nonproprietary Names can be found in Cumulative List No. 15, 2011 (available in CD-ROM only). Dénominations communes internationales des Substances pharmaceutiques (DCI) Dénominations communes internationales RECOMMANDÉES: Liste 73 Il est notifié que, conformément aux dispositions du paragraphe 7 de la Procédure à suivre en vue du choix de Dénominations communes internationales recommandées pour les Substances pharmaceutiques [Actes off. Org. mond. Santé, 1955, 60, 3 (résolution EB15.R7); 1969, 173, 10 (résolution EB43.R9); résolution EB115.R4 (EB115/2005/REC/1)] les dénominations ci-dessous sont choisies par l’Organisation mondiale de la Santé en tant que dénominations communes internationales recommandées. L’inclusion d’une dénomination dans les listes de DCI recommandées n’implique aucune recommandation en vue de l’utilisation de la substance correspondante en médecine ou en pharmacie. On trouvera d’autres listes de Dénominations communes internationales proposées (1–109) et recommandées (1–70) dans la Liste récapitulative No. 15, 2013 (disponible sur CD-ROM seulement). Denominaciones Comunes Internacionales para las Sustancias Farmacéuticas (DCI) Denominaciones Comunes Internacionales RECOMENDADAS: Lista 73 De conformidad con lo que dispone el párrafo 7 del Procedimiento de Selección de Denominaciones Comunes Internacionales Recomendadas para las Sustancias Farmacéuticas [Act. Of. Mund. Salud, 1955, 60, 3 (Resolución EB15.R7); 1969, 173, 10 (Resolución EB43.R9); Résolution EB115.R4 (EB115/2005/REC/1) EB115.R4 (EB115/2005/REC/1)], se comunica por el presente anuncio que las denominaciones que a continuación se expresan han sido seleccionadas como Denominaciones Comunes Internacionales Recomendadas. La inclusión de una denominación en las listas de las Denominaciones Comunes Recomendadas no supone recomendación alguna en favor del empleo de la sustancia respectiva en medicina o en farmacia. Las listas de Denominaciones Comunes Internacionales Propuestas (1–109) y Recomendadas (1–70) se encuentran reunidas en Cumulative List No. 15, 2013 (disponible sólo en CD-ROM). Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 62 Latin, English, French, Spanish: Recommended INN DCI Recommandée DCI Recomendada Chemical name or description; Molecular formula; Graphic formula Nom chimique ou description; Formule brute; Formule développée Nombre químico o descripción; Fórmula molecular; Fórmula desarrollada abrilumabum # abrilumab immunoglobulin G2-kappa, anti-[Homo sapiens integrin ITGA4_ITGB7 (integrin alpha4 (CD49d)_beta7, integrin α4β7, lymphocyte Peyer's patch adhesion molecule 1, LPAM-1)], Homo sapiens monoclonal antibody; gamma2 heavy chain (1-444) [Homo sapiens VH(IGHV1- 24*01 (94.90%) -(IGHD)-IGHJ5*02) [8.8.11] (1-118) - IGHG2*01 (CH1 (119-216), hinge (217-228), CH2 (229- 337), CH3 (338-442), CHS (443-444)) (119-444)], (132- 214')-disulfide with kappa light chain (1'-214') [Homo sapiens V-KAPPA (IGKV1-12*01 (95.80%) -IGKJ1*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dimer (220- 220'':221-221'':224-224'':227-227'')-tetrakisdisulfide abrilumab immunoglobuline G2-kappa, anti-[Homo sapiens intégrine ITGA4_ITGB7 (intégrine alpha4 (CD49d)_bêta7, intégrine α4β7, récepteur d’adressage spécifique des plaques de Peyer, LPAM-1)], Homo sapiens anticorps monoclonal; chaîne lourde gamma2 (1-444) [Homo sapiens (IGHV1- 24*01 (94.90%) -(IGHD)-IGHJ5*02) [8.8.11] (1-118) - IGHG2*01 (CH1 (119-216), charnière (217-228), CH2 (229-337), CH3 (338-442), CHS (443-444)) (119-444)], (132-214')-disulfure avec la chaîne légère kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1-12*01 (95.80%) - IGKJ1*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dimère(220-220'':221-221'':224-224'':227-227'')- tétrakisdisulfure abrilumab inmunoglobulina G2-kappa, anti-[Homo sapiens integrina ITGA4_ITGB7 (integrina alfa4 (CD49d)_beta7, integrina α4β7, molécula de adhesión específica de linfocitos de las placas de Peyer, LPAM-1)], anticuerpo monoclonal de Homo sapiens; cadena pesada gamma2 (1-444) [Homo sapiens (IGHV1- 24*01 (94.90%) -(IGHD)-IGHJ5*02) [8.8.11] (1-118) - IGHG2*01 (CH1 (119-216), bisagra (217-228), CH2 (229- 337), CH3 (338-442), CHS (443-444)) (119-444)], (132- 214')-disulfuro con la cadena ligera kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1-12*01 (95.80%) -IGKJ1*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dímero(220- 220'':221-221'':224-224'':227-227'')-tetrakisdisulfuro WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 63 Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKVSGYTLS DLSIHWVRQA PGKGLEWMGG 50 FDPQDGETIY AQKFQGRVTM TEDTSTDTAY MELSSLKSED TAVYYCATGS 100 SSSWFDPWGQ GTLVTVSSAS TKGPSVFPLA PCSRSTSEST AALGCLVKDY 150 FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSNFGTQTYT 200 CNVDHKPSNT KVDKTVERKC CVECPPCPAP PVAGPSVFLF PPKPKDTLMI 250 SRTPEVTCVV VDVSHEDPEV QFNWYVDGVE VHNAKTKPRE EQFNSTFRVV 300 SVLTVVHQDW LNGKEYKCKV SNKGLPAPIE KTISKTKGQP REPQVYTLPP 350 SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPMLDSDGS 400 FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK 444 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS VSASVGDRVT ITCRASQGIS SWLAWYQQKP GKAPKLLIYG 50 ASNLESGVPS RFSGSGSGTD FTLTISSLQP EDFANYYCQQ ANSFPWTFGQ 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 145-201 258-318 364-422 22''-96'' 145''-201'' 258''-318'' 364''-422'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (CH1 10-CL 126) 132-214' 132''-214''' Inter-H-H (h 4, h 5, h 8, h 11) 220-220'' 221-221'' 224-224'' 227-227'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 294, 294'' acorafloxacinum acorafloxacin 7-[(3E)-3-(2-amino-1-fluoroethylidene)piperidin-1-yl]- 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo- 1,4-dihydroquinoline-3-carboxylic acid acorafloxacine acide 7-[(3E)-3-(2-amino-1-fluoroéthylidène)pipéridin-1-yl]- 1-cyclopropyl-6-fluoro-8-méthoxy-4-oxo- 1,4-dihydroquinoléine-3-carboxylique acorafloxacino ácido 7-[(3E)-3-(2-amino-1-fluoroetilideno)piperidin-1-il]- 1-ciclopropil-6-fluoro-8-metoxi-4-oxo-1,4-dihidroquinolina- 3-carboxílico C21H23F2N3O4 N O OCH3 F CO2H NF H2N acumapimodum acumapimod 3-[5-amino-4-(3-cyanobenzoyl)-1H-pyrazol-1-yl]- N-cyclopropyl-4-methylbenzamide acumapimod 3-[5-amino-4-(3-cyanobenzoyl)-1H-pyrazol-1-yl]- N-cyclopropyl-4-méthylbenzamide acumapimod 3-[5-amino-4-(3-cianobenzoil)-1H-pirazol-1-il]-N-ciclopropil- 4-metilbenzamida Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 64 C22H19N5O2 N CH3 N H O N NH2 O N albenatidum # albenatide S3.34-{1-[(23S)-23-{[exendin-4 Heloderma suspectum precursor-(48-86)-peptidyl (exenatidyl)]amino}-3,12,24- trioxo-7,10-dioxa-4,13,18,25-tetraazapentacosyl]- 2,5-dioxopyrrolidin-3-yl}human serum albumin. Peptide is synthetic, and human serum albumin is produced in Saccharomyces cerevisiae. albénatide S3.34-{1-[(23S)-23-{[précurseur de l’exendin-4 de Heloderma suspectum-(48-86)-peptidyl (exénatidyl)]amino}-3,12,24-trioxo-7,10-dioxa-4,13,18,25- tétraazapentacosyl]-2,5-dioxopyrrolidin-3-yl}albumine sérique humaine. Le peptide est synthétique et l'albumine sérique humaine est produite par Saccharomyces cerevisiae. albenatida S3.34-{1-[(23S)-23-{[precursor de la exendina-4 de Heloderma suspectum-(48-86)-peptidil (exenatidil)]amino}- 3,12,24-trioxo-7,10-dioxa-4,13,18,25-tetraazapentacosil]- 2,5-dioxopirrolidin-3-il}albúmina sérica humana. El péptido es sintético y la albúmina sérica humana la produce el Saccharomyces cerevisiae. HN O O O H N O N H N S H O O H H2N CO2H H N H O NH2R R = exenatidyl H2N CO2H HO P OHO HO H2N CO2H H O H P O HO HO H3C Human Albumin / Albumine humaine / Albumina humana DAHKSEVAHR FKDLGEENFK ALVLIAFAQY LQQCPFEDHV KLVNEVTEFA 50 KTCVADESAE NCDKSLHTLF GDKLCTVATL RETYGEMADC CAKQEPERNE 100 CFLQHKDDNP NLPRLVRPEV DVMCTAFHDN EETFLKKYLY EIARRHPYFY 150 APELLFFAKR YKAAFTECCQ AADKAACLLP KLDELRDEGK ASSAKQRLKC 200 ASLQKFGERA FKAWAVARLS QRFPKAEFAE VSKLVTDLTK VHTECCHGDL 250 LECADDRADL AKYICENQDS ISSKLKECCE KPLLEKSHCI AEVENDEMPA 300 DLPSLAADFV ESKDVCKNYA EAKDVFLGMF LYEYARRHPD YSVVLLLRLA 350 KTYETTLEKC CAAADPHECY AKVFDEFKPL VEEPQNLIKQ NCELFEQLGE 400 YKFQNALLVR YTKKVPQVST PTLVEVSRNL GKVGSKCCKH PEAKRMPCAE 450 DYLSVVLNQL CVLHEKTPVS DRVTKCCTES LVNRRPCFSA LEVDETYVPK 500 EFNAETFTFH ADICTLSEKE RQIKKQTALV ELVKHKPKAT KEQLKAVMDD 550 FAAFVEKCCK ADDKETCFAE EGKKLVAASQ AALGL 585 Exenatidyl / Exénatidyl / Exenatidil HGEGTFTSDL SKQMEEEAVR LFIEWLKNGG PSSGAPPPS- 39 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 53-62 75-91 90-101 124-169 168-177 200-246 245-253 265-279 278-289 316-361 360-369 392-438 437-448 461-477 476-487 514-559 558-567 Modified residues / Résidus modifiés / Restos modificados C 34 Exenatidyl- Lys-linker-Cys S 58 , 419 phosphoSer T 420 , 422 phosphoThr WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 65 asvasiranum asvasiran small interfering ARN (siRNA) inhibitor of human Respiratory Syncytial Virus replication; duplex of guanylyl-(3'→5')-guanylyl-(3'→5')-cytidylyl- (3'→5')-uridylyl-(3'→5')-cytidylyl-(3'→5')-uridylyl-(3'→5')- uridylyl-(3'→5')-adenylyl-(3'→5')-guanylyl-(3'→5')-cytidylyl- (3'→5')-adenylyl-(3'→5')-adenylyl-(3'→5')-adenylyl-(3'→5')- guanylyl-(3'→5')-uridylyl-(3'→5')-cytidylyl-(3'→5')-adenylyl- (3'→5')-adenylyl-(3'→5')-guanylyl-(3'→5')-thymidylyl- (3'→5')-thymidine and thymidylyl-(5'→3')-thymidylyl- (5'→3')-cytidylyl-(5'→3')-cytidylyl-(5'→3')-guanylyl-(5'→3')- adenylyl-(5'→3')-guanylyl-(5'→3')-adenylyl-(5'→3')- adenylyl-(5'→3')-uridylyl-(5'→3')-cytidylyl-(5'→3')-guanylyl- (5'→3')-uridylyl-(5'→3')-uridylyl-(5'→3')-uridylyl-(5'→3')- cytidylyl-(5'→3')-adenylyl-(5'→3')-guanylyl-(5'→3')-uridylyl- (5'→3')-uridylyl-(5'→3')-cytidine asvasiran petit ARN interférant (siRNA) inhibiteur de la réplication du virus respiratoire syncytial humain; duplex de guanylyl-(3'→5')-guanylyl-(3'→5')-cytidylyl- (3'→5')-uridylyl-(3'→5')-cytidylyl-(3'→5')-uridylyl-(3'→5')- uridylyl-(3'→5')-adénylyl-(3'→5')-guanylyl-(3'→5')-cytidylyl- (3'→5')-adénylyl-(3'→5')-adénylyl-(3'→5')-adénylyl-(3'→5')- guanylyl-(3'→5')-uridylyl-(3'→5')-cytidylyl-(3'→5')-adénylyl- (3'→5')-adénylyl-(3'→5')-guanylyl-(3'→5')-thymidylyl- (3'→5')-thymidine et de thymidylyl-(5'→3')-thymidylyl- (5'→3')-cytidylyl-(5'→3')-cytidylyl-(5'→3')-guanylyl-(5'→3')- adénylyl-(5'→3')-guanylyl-(5'→3')-adénylyl-(5'→3')- adénylyl-(5'→3')-uridylyl-(5'→3')-cytidylyl-(5'→3')-guanylyl- (5'→3')-uridylyl-(5'→3')-uridylyl-(5'→3')-uridylyl-(5'→3')- cytidylyl-(5'→3')-adénylyl-(5'→3')-guanylyl-(5'→3')-uridylyl- (5'→3')-uridylyl-(5'→3')-cytidine asvasirán ARN pequeño de interferencia (ARNip) (siRNA) inhibidor de la replicación del virus respiratorio sincitial humano; duplex de guanilil-(3'→5')-guanilil-(3'→5')-citidilil-(3'→5')- uridilil-(3'→5')-citidilil-(3'→5')-uridilil-(3'→5')-uridilil-(3'→5')- adenilil-(3'→5')-guanilil-(3'→5')-citidilil-(3'→5')-adenilil- (3'→5')-adenilil-(3'→5')-adenilil-(3'→5')-guanilil-(3'→5')- uridilil-(3'→5')-citidilil-(3'→5')-adenilil-(3'→5')-adenilil- (3'→5')-guanilil-(3'→5')-timidilil-(3'→5')-timidina y de timidilil-(5'→3')-timidilil-(5'→3')-citidilil-(5'→3')-citidilil- (5'→3')-guanilil-(5'→3')-adenilil-(5'→3')-guanilil-(5'→3')- adenilil-(5'→3')-adenilil-(5'→3')-uridilil-(5'→3')-citidilil- (5'→3')-guanilil-(5'→3')-uridilil-(5'→3')-uridilil-(5'→3')-uridilil- (5'→3')-citidilil-(5'→3')-adenilil-(5'→3')-guanilil-(5'→3')- uridilil-(5'→3')-uridilil-(5'→3')-citidina C401H500N150O290P40 [(3’-5’)-G-G-C-U-C-U-U-A-G-C-A-A-A-G-U-C-A-A-G-dT-dT] . . . . . . . . . . . . . . . . . . . [(5’-3’)-dT-dT-C-C-G-A-G-A-A-U-C-G-U-U-U-C-A-G-U-U-C] Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 66 azeliragonum azeliragon 3-(4-{2-butyl-1-[4-(4-chlorophenoxy)phenyl]-1H-imidazol- 4-yl}phenoxy)-N,N-diethylpropan-1-amine azéliragon 3-(4-{2-butyl-1-[4-(4-chlorophénoxy)phényl]-1H-imidazol- 4-yl}phénoxy)-N,N-diéthylpropan-1-amine azeliragón 3-(4-{2-butil-1-[4-(4-clorofenoxi)fenil]-1H-imidazol- 4-il}fenoxi)-N,N-dietilpropan-1-amina C32H38ClN3O2 N O Cl NH3C O N CH3 CH3 basmisanilum basmisanil (1,1-dioxo-1λ6-thiomorpholin-4-yl)(6-{[3-(4-fluorophenyl)- 5-methyl-1,2-oxazol-4-yl]methoxy}pyridin-3-yl)methanone basmisanil (1,1-dioxo-1λ6-thiomorpholin-4-yl)(6-{[3-(4-fluorophényl)- 5-méthyl-1,2-oxazol-4-yl]méthoxy}pyridin-3-yl)méthanone basmisanil (1,1-dioxo-1λ6-tiomorfolin-4-il)(6-{[3-(4-fluorofenil)-5-metil- 1,2-oxazol-4-il]metoxi}piridin-3-il)metanona C21H20FN3O5S N N S ON O CH3 F O O O beclabuvirum beclabuvir (4bS,5aR)-12-cyclohexyl-N-(dimethylsulfamoyl)- 3-methoxy-5a-[(3-methyl-3,8-diazabicyclo[3.2.1]oct- 8-yl)carbonyl]-4b,5,5a,6-tetrahydrocyclopropa[d]indolo[2,1- a][2]benzazepine-9-carboxamide béclabuvir (4bS,5aR)-12-cyclohexyl-N-(diméthylsulfamoyl)- 3-méthoxy-5a-[(3-méthyl-3,8-diazabicyclo[3.2.1]oct- 8-yl)carbonyl]-4b,5,5a,6-tétrahydrocyclopropa[d]indolo[2,1- a][2]benzazépine-9-carboxamide beclabuvir (4bS,5aR)-12-ciclohexil-N-(dimetilsulfamoil)-3-metoxi- 5a-[(3-metil-3,8-diazabiciclo[3.2.1]oct-8-il)carbonil]- 4b,5,5a,6-tetrahidrociclopropa[d]indolo[2,1- a][2]benzazepina-9-carboxamida WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 67 C36H45N5O5S N H3CO H O N N CH3 O N H S N OO CH3 CH3 begelomabum # begelomab immunoglobulin G2b-kappa, anti-[Homo sapiens DPP4(dipeptidyl-peptidase 4, dipeptidylpeptidase IV, adenosine deaminase complexing protein 2, ADCP2, TP103, T cell activation antigen CD26, CD26)], Mus musculus monoclonal antibody; gamma2b heavy chain (1-456) [Mus musculus VH (IGHV1- 85*01 (88.80%) -(IGHD)-IGHJ1*01) [8.8.13] (1-120) - IGHG2B*02 (CH1 (121-217), hinge (218-239), CH2 (240- 349), CH3 (350-454), CHS (455-456)) (121-456)], (135- 213')-disulfide with kappa light chain (1'-213') [Mus musculus V-KAPPA (IGKV4-57*01 (98.90%) -IGKJ1*01) [5.3.9] (1'-106') -IGKC*01 (107'-213')]; dimer (229- 229'':232-232'':235-235'':238-238'')-tetrakisdisulfide bégélomab immunoglobuline G2b-kappa, anti-[Homo sapiens DPP4 (dipeptidyl-peptidase 4, dipeptidylpeptidase IV, protéine 2 complexant l’adénosine désaminase, ADCP2, TP103, antigène CD26 d’activation des cellules T, CD26)], Mus musculus anticorps monoclonal; chaîne lourde gamma2b (1-456) [Mus musculus VH (IGHV1-85*01 (88.80%) -(IGHD)-IGHJ1*01) [8.8.13] (1- 120) -IGHG2B*02 (CH1 (121-217), charnière (218-239), CH2 (240-349), CH3 (350-454), CHS (455-456)) (121- 456)], (135-213')-disulfure avec la chaîne légère kappa (1'- 213') [Mus musculusV-KAPPA (IGKV4-57*01 (98.90%) - IGKJ1*01) [5.3.9] (1'-106') -IGKC*01 (107'-213')]; dimère (229-229'':232-232'':235-235'':238-238'')-tétrakisdisulfure begelomab inmunoglobulina G2b-kappa, anti-[Homo sapiens DPP4 (dipeptidil-peptidasa 4, dipeptidilpeptidasa IV, proteína 2 complejante de la adenosina desaminasa, ADCP2, TP103, antígeno CD26 de activación de las células T, CD26)], anticuerpo monoclonal de Mus musculus ; cadena pesada gamma2b (1-456) [Mus musculus VH (IGHV1-85*01 (88.80%) -(IGHD)-IGHJ1*01) [8.8.13] (1- 120) -IGHG2B*02 (CH1 (121-217), bisagra (218-239), CH2 (240-349), CH3 (350-454), CHS (455-456)) (121-456)], (135-213')-disulfuro con la cadena ligera kappa (1'-213') [Mus musculus V-KAPPA (IGKV4-57*01 (98.90%) - IGKJ1*01) [5.3.9] (1'-106') -IGKC*01 (107'-213')]; dímero (229-229'':232-232'':235-235'':238-238'')-tetrakisdisulfuro Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 68 Heavy chain / Chaîne lourde / Cadena pesadaQVQLQQSGAE LVKPGASVKL SCKASGYTFR SYDINWVRQR PEQGLEWIGW 50 IFPGDGSTKY NEKFKGKATL TTDKSSSTAY MQLSRLTSED SAVYFCARWT 100 VVGPGYFDVW GAGTTVTVSS AKTTPPSVYP LAPGCGDTTG SSVTLGCLVK 150 GYFPESVTVT WNSGSLSSSV HTFPALLQSG LYTMSSSVTV PSSTWPSQTV 200 TCSVAHPASS TTVDKKLEPS GPISTINPCP PCKECHKCPA PNLEGGPSVF 250 IFPPNIKDVL MISLTPKVTC VVVDVSEDDP DVQISWFVNN VEVHTAQTQT 300 HREDYNSTIR VVSTLPIQHQ DWMSGKEFKC KVNNKDLPSP IERTISKIKG 350 LVRAPQVYIL PPPAEQLSRK DVSLTCLVVG FNPGDISVEW TSNGHTEENY 400 KDTAPVLDSD GSYFIYSKLN MKTSKWEKTD SFSCNVRHEG LKNYYLKKTI 450 SRSPGK 456 Light chain / Chaîne légère / Cadena ligera QIVLTQSPAI MSASPGEKVT ITCSASSSVS YMNWFQQKPG TSPKLWIYST 50 SNLASGVPAR FSGSGSGTSY SLTISRMEAE DAATYYCQQR SSYPNTFGGG 100 TKLEIKRADA APTVSIFPPS SEQLTSGGAS VVCFLNNFYP KDINVKWKID 150 GSERQNGVLN SWTDQDSKDS TYSMSSTLTL TKDEYERHNS YTCEATHKTS 200 TSPIVKSFNR NEC 213 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 147-202 270-330 376-434 22''-96'' 147''-202'' 270''-330'' 376''-434'' Intra-L (C23-C104) 23'-87' 133'-193' 23'''-87''' 133'''-193''' Inter-H-L (CH1 11-CL 126) 135-213' 135''-213''' Inter-H-H (h 12, h 15, h 18, h 21) 229-229'' 232-232'' 235-235'' 238-238'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 306, 306'' benzhydrocodonum benzhydrocodone 4,5α-epoxy-3-methoxy-17-methyl-6,7-didehydromorphinan- 6-yl benzoate benzhydrocodone benzoate de 4,5α-époxy-3-méthoxy-17-méthyl- 6,7-didéhydromorphinan-6-yle benzhidrocodona benzoato de 4,5α-epoxi-17-metil-3-metoxi- 6,7-dideshidromorfinan-6-ilo C25H25NO4 N O HH3CO CH3 H H O O bradaniclinum bradanicline N-[(2S,3R)-2-[(pyridin-3-yl)methyl]-1-azabicyclo[2.2.2]oct- 3-yl]-1-benzofuran-2-carboxamide bradanicline N-[(2S,3R)-2-(pyridin-3-ylméthyl)-1-azabicyclo[2.2.2]oct- 3-yl]-1-benzofurane-2-carboxamide bradaniclina N-[(2S,3R)-2-(piridin-3-ilmetil)-1-azabiciclo[2.2.2]oct-3-il]- 1-benzofurano-2-carboxamida WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 69 C22H23N3O2 N N H O O H H N briciclibum briciclib 2-methoxy-5-({[(E)-2-(2,4,6- trimethoxyphenyl)ethenyl]sulfonyl}methyl)phenyl dihydrogen phosphate briciclib dihydrogénophosphate de 2-méthoxy-5-({[2-(2,4,6- triméthoxyphényl)éthényl]sulfonyl}méthyl)phenyl briciclib dihidrógenofosfato de 2-metoxi-5-({[2-(2,4,6- trimetoxifenil)etenil]sulfonil}metil)fenilo C19H23O10PS OCH3 OCH3 H3CO S O O O OCH3 P O OH OH brontictuzumabum # brontictuzumab immunoglobulin G2-lambda, anti-[Homo sapiens NOTCH1 (Notch 1, Translocation-associated notch-1, TAN- 1,TAN1)], humanized monoclonal antibody; gamma2 heavy chain (1-447) [humanized VH (Homo sapiens IGHV1-24*01 (80.40%) -(IGHD)-IGHJ4*01 L123>T (116)) [8.8.14] (1-121) -Homo sapiens IGHG2*01 (CH1 (122-219), hinge (220-231), CH2 (232-340), CH3 (341- 445), CHS (446-447)) (122-447)],(135-214')-disulfide with lambda light chain (1'-215’) [humanized V-LAMBDA (Homo sapiens IGLV7-46*01 (83.20%) -IGLJ2*01) [9.3.9] (1'-109') -Homo sapiens IGLC7*01 (110'-215')]; dimer (223- 223'':224-224'':227-227'':230-230'')-tetrakisdisulfide brontictuzumab immunoglobuline G2-lambda, anti-[Homo sapiens NOTCH1 (Notch 1, notch-1 associé aux translocations, TAN-1,TAN1)], anticorps monoclonal humanisé; chaîne lourde gamma2 (1-447) [VH humanisé (Homo sapiens IGHV1-24*01 (80.40%) -(IGHD)-IGHJ4*01 L123>T (116)) [8.8.14] (1-121) -Homo sapiens IGHG2*01 (CH1 (122-219), charnière (220-231), CH2 (232-340), CH3 (341- 445), CHS (446-447)) (122-447)], (135-214')-disulfure avec la chaîne légère lambda (1'-215') [V-LAMBDA humanisé (Homo sapiens IGLV7-46*01 (83.20%) -IGLJ2*01) [9.3.9] (1'-109') -Homo sapiens IGLC7*01 (110'-215')]; dimère (223-223'':224-224'':227-227'':230-230'')-tétrakisdisulfure Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 70 brontictuzumab inmunoglobulina G2-lambda, anti-[NOTCH1 de Homo sapiens (Notch 1, notch-1 asociado a las translocaciones, TAN-1,TAN1)], anticuerpo monoclonal humanizado; cadena pesada gamma2 (1-447) [VH humanizado (Homo sapiens IGHV1-24*01 (80.40%) -(IGHD)-IGHJ4*01 L123>T (116)) [8.8.14] (1-121) -Homo sapiens IGHG2*01 (CH1 (122-219), bisagra (220-231), CH2 (232-340), CH3 (341- 445), CHS (446-447)) (122-447)], (135-214')-disulfuro con la cadena ligera lambda (1'-215') [V-LAMBDA humanizada (Homo sapiens IGLV7-46*01 (83.20%) -IGLJ2*01) [9.3.9] (1'-109') -Homo sapiens IGLC7*01 (110'-215')]; dímero (223-223'':224-224'':227-227'':230-230'')-tetrakisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKI SCKVSGYTLR GYWIEWVRQA PGKGLEWIGQ 50 ILPGTGRTNY NEKFKGRVTM TADTSTDTAY MELSSLRSED TAVYYCARFD 100 GNYGYYAMDY WGQGTTVTVS SASTKGPSVF PLAPCSRSTS ESTAALGCLV 150 KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSNFGTQ 200 TYTCNVDHKP SNTKVDKTVE RKCCVECPPC PAPPVAGPSV FLFPPKPKDT 250 LMISRTPEVT CVVVDVSHED PEVQFNWYVD GVEVHNAKTK PREEQFNSTF 300 RVVSVLTVVH QDWLNGKEYK CKVSNKGLPA PIEKTISKTK GQPREPQVYT 350 LPPSREEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPMLDS 400 DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK 447 Light chain / Chaîne légère / Cadena ligera QAVVTQEPSL TVSPGGTVTL TCRSSTGAVT TSNYANWFQQ KPGQAPRTLI 50 GGTNNRAPGV PARFSGSLLG GKAALTLSGA QPEDEAEYYC ALWYSNHWVF 100 GGGTKLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLVS DFYPGAVTVA 150 WKADGSPVKV GVETTKPSKQ SNNKYAASSY LSLTPEQWKS HRSYSCRVTH 200 EGSTVEKTVA PAECS 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 148-204 261-321 367-425 22''-96'' 148''-204'' 261''-321'' 367''-425'' Intra-L (C23-C104) 22'-90' 137'-196' 22'''-90''' 137'''-196''' Inter-H-L (CH1 10-CL 126) 135-214' 135''-214''' Inter-H-H (h 4, h 5, h 8, h 11) 223-223'' 224-224'' 227-227'' 230-230'' Possible other H-L and H-H crosslinks Inter-H-L 223-214' 223''-214''' Inter-H-H 135-224'' 135''-224 227-227'' 230-230'' Possible other H-L and H-H crosslinks Inter-H-L 135-214' 223''-214''' Inter-H-H 223-135'' 224-224'' 227-227'' 230-230'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 297, 297'' butylphthalidum butylphthalide rac-3-butyl-2-benzofuran-1(3H)-one butylphthalide rac-3-butyl-2-benzofuran-1(3H)-one butilftalida rac-3-butil-2-benzofuran-1(3H)-ona C12H14O2 and enantiomer et énantiomère y enantiómero O O H CH3 cabotegravirum cabotegravir (3S,11aR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy- 3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2- a]pyrido[1,2-d]pyrazine-8-carboxamide WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 71 cabotégravir (3S,11aR)-N-[(2,4-difluorophényl)méthyl]-6-hydroxy- 3-méthyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2- a]pyrido[1,2-d]pyrazine-8-carboxamide cabotegravir (3S,11aR)-N-[(2,4-difluorofenil)metil]-6-hidroxi-3-metil- 5,7-dioxo-2,3,5,7,11,11a-hexahidrooxazolo[3,2- a]pirido[1,2-d]pirazina-8-carboxamida C19H17F2N3O5 N N O OH O H N F F O O H CH3H capmatinibum capmatinib 2-fluoro-N-methyl-4-{7-[(quinolin-6-yl)methyl]imidazo[1,2- b][1,2,4]triazin-2-yl}benzamide capmatinib 2-fluoro-N-méthyl-4-{7-[(quinoléin-6-yl)méthyl]imidazo[1,2- b][1,2,4]triazin-2-yl}benzamide capmatinib 2-fluoro-N-metil-4-{7-[(quinolein-6-il)metil]imidazo[1,2- b][1,2,4]triazin-2-il}benzamida C23H17FN6O F N N NN N O N H CH3 cefilavancinum cefilavancin (6R,7R)-7-[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-({3- [(3S,6R,7R,22R,23S,26S,30aSa,36R,38aR)-3-(2-amino- 2-oxoethyl)-44-{[2-O-(3-amino-2,3,6-trideoxy-3-C-methyl- α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyl]oxy}- 10,19-dichloro-7,22,28,30,32-pentahydroxy-6-[(N-methyl- D-leucyl)amino]-2,5,24,38,39-pentaoxo- 2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tetradecahydro- 1H,22H-8,11:18,21-dietheno-23,36-(iminomethano)- 13,16:31,35-dimetheno[1,6,9]oxadiazacyclohexadecino [4,5-m][10,2,16]benzoxadiazacyclotetracosine- 26-carboxamido]propoxy}imino)acetamido]-8-oxo- 3-[(pyridin-1-ium-1-yl)methyl]-5-thia-1-azabicyclo[4.2.0]oct- 2-ene-2-carboxylate Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 72 céfilavancine (6R,7R)-7-[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-({3- [(3S,6R,7R,22R,23S,26S,30aSa,36R,38aR)-3-(2-amino- 2-oxoéthyl)-44-{[2-O-(3-amino-2,3,6-tridéoxy-3-C-méthyl- α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyl]oxy}- 10,19-dichloro-7,22,28,30,32-pentahydroxy-6-[(N-méthyl- D-leucyl)amino]-2,5,24,38,39-pentaoxo- 2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tétradécahydro- 1H,22H-8,11:18,21-diéthéno-23,36-(iminométhano)- 13,16:31,35-diméthéno[1,6,9]oxadiazacyclohexadécino [4,5-m][10,2,16]benzoxadiazacyclotétracosine- 26-carboxamido]propoxy}imino)acétamido]-8-oxo- 3-[(pyridin-1-ium-1-yl)méthyl]-5-thia-1-azabicyclo[4.2.0]oct- 2-ène-2-carboxylate cefilavancina (6R,7R)-7-[(2Z)-2-(2-amino-5-cloro-1,3-tiazol-4-il)-2-({3- [(3S,6R,7R,22R,23S,26S,30aSa,36R,38aR)-3-(2-amino- 2-oxoetil)-44-{[2-O-(3-amino-2,3,6-tridesoxi-3-C-metil- α-L-lixo-hexopiranosil)-β-D-glucopiranosil]oxi}- 10,19-dicloro-7,22,28,30,32-pentahidroxi-6-[(N-metil- D-leucil)amino]-2,5,24,38,39-pentaoxo- 2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tetradecahidro- 1H,22H-8,11:18,21-dieteno-23,36-(iminometano)- 13,16:31,35-dimeteno[1,6,9]oxadiazaciclohexadecino [4,5-m][10,2,16]benzoxadiazaciclotetracosina- 26-carboxamido]propoxi}imino)acetamido]-8-oxo- 3-[(piridin-1-io-1-il)metil]-5-tia-1-azabiciclo[4.2.0]oct-2-eno- 2-carboxilato C87H95Cl3N16O28S2 HN O OHN NH HN NH HN O O O O HO H H O HO OH HO H2N O OH HH Cl H H H O O O O NH2H3C OH CH3 OH OH HO H HN N S CO2 O H N O N O H H N O CH3 CH3 NH H H3C O Cl N S Cl H2N cerdulatinibum cerdulatinib 4-(cyclopropylamino)-2-({4-[4-(ethanesulfonyl)piperazin- 1-yl]phenyl}amino)pyrimidine-5-carboxamide WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 73 cerdulatinib 4-(cyclopropylamino)-2-({4-[4-(éthanesulfonyl)pipérazin- 1-yl]phényl}amino)pyrimidine-5-carboxamide cerdulatinib 4-(ciclopropilamino)-2-({4-[4-(etanosulfonil)piperazin- 1-il]fenil}amino)pirimidina-5-carboxamida C20H27N7O3S N N N H H2N O HN N N S OO CH3 cerliponasum alfa # cerliponase alfa immature human tripeptidyl-peptidase 1 (cell growth- inhibiting gene 1 protein, lysosomal pepstatin-insensitive protease, TPP-1, EC 3.4.14.9), 544 residues protein, produced in Chinese hamster ovary (CHO) cells, glycoform alfa cerliponase alfa tripeptidyl-peptidase 1 humaine immature (protéine du gène 1 inhibitrice du développement cellulaire, protéase lysosomiale non-contrôlée par la pepstatine, TPP-1, EC 3.4.14.9), protéine de 544 résidus, produite par des cellules ovariennes de hamster chinois, forme glycosylée alfa cerliponasa alfa tripeptidil-peptidasa 1 humana inmadura (proteína del gen 1 inhibidora del desarrollo celular, proteasa lisosomial no controlada por la pepstatina, TPP-1, EC 3.4.14.9), proteína de 544 restos, producida por células ováricas de hamster chino, forma glicosilada alfa C2657H4042N734O793S11 Sequence / Séquence / SecuenciaSYSPEPDQRR TLPPGWVSLG RADPEEELSL TFALRQQNVE RLSELVQAVS 50 DPSSPQYGKY LTLENVADLV RPSPLTLHTV QKWLLAAGAQ KCHSVITQDF 100 LTCWLSIRQA ELLLPGAEFH HYVGGPTETH VVRSPHPYQL PQALAPHVDF 150 VGGLHRFPPT SSLRQRPEPQ VTGTVGLHLG VTPSVIRKRY NLTSQDVGSG 200 TSNNSQACAQ FLEQYFHDSD LAQFMRLFGG NFAHQASVAR VVGQQGRGRA 250 GIEASLDVQY LMSAGANIST WVYSSPGRHE GQEPFLQWLM LLSNESALPH 300 VHTVSYGDDE DSLSSAYIQR VNTELMKAAA RGLTLLFASG DSGAGCWSVS 350 GRHQFRPTFP ASSPYVTTVG GTSFQEPFLI TNEIVDYISG GGFSNVFPRP 400 SYQEEAVTKF LSSSPHLPPS SYFNASGRAY PDVAALSDGY WVVSNRVPIP 450 WVSGTSASTP VFGGILSLIN EHRILSGRPP LGFLNPRLYQ QHGAGLFDVT 500 RGCHESCLDE EVEGQGFCSG PGWDPVTGWG TPNFPALLKT LLNP 544 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 92-103 346-507 503-518 Glycosylation sites (N)/ Sites de glycosylation (N) / Posiciones de glicosilación (N) Asn-191 Asn-203 Asn-267 Asn-294 Asn-424 dagrocoratum dagrocorat (4bS,7R,8aR)-4b-benzyl-7-hydroxy-N-(2-methylpyridin- 3-yl)-7-(trifluoromethyl)-4b,5,6,7,8,8a,9,10- octahydrophenanthrene-2-carboxamide dagrocorat (4bS,7R,8aR)-4b-benzyl-7-hydroxy-N-(2-méthylpyridin- 3-yl)-7-(trifluorométhyl)-4b,5,6,7,8,8a,9,10- octahydrophénanthrène-2-carboxamide Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 74 dagrocorat (4bS,7R,8aR)-4b-bencil-7-hidroxi-N-(2-metilpiridin-3-il)- 7-(trifluorometil)-4b,5,6,7,8,8a,9,10-octahidrofenantreno- 2-carboxamida C29H29F3N2O2 H N N CH3 O H CF3 OH dalazatidum dalazatide a 37-residue, synthetic peptide derivative of the Stichodactyla toxin: O-phosphono-L-tyrosyl-2-[2-(2- aminoethoxy)ethoxy]acetyl[potassium channel toxin kappa- stichotoxin-Shela Stoichactis helianthus (Caribbean sea anemone)] peptidamide dalazatide peptide sythétique de 37 acides aminés dérivé de la toxine extraite de Stichodactyla: O-phosphono-L-tyrosyl-2-[2-(2- aminoéthoxy)éthoxy]acétyl[toxine kappa du canal potassique-stichotoxine-Shela Stoichactis helianthus (anémone de mer des Antilles)] peptidamide dalazatida péptido sintético de 37 aminoácidos derivado de la toxina extraída de Stichodactyla: O-fosfono-L-tirosil-2-[2-(2-aminoetoxi)etoxi]acetil[toxina kappa del canal de potasio-stichotoxina-Shela Stoichactis helianthus (anémona del Mar de las Antillas)] peptidamida C184H296N57O55PS7 H2N H NH2 O HS CO2H O P HO NH2H O OH O O CO2HH2N Sequence / Séquence / Secuencia YXRSCIDTIP KSRCTAFQCK HSMKYRLSFC RKTCGTC 37 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 5-37 14-30 19-34 Modified residues / Résidus modifiés / Restos modificados X (2) 2-[2-(2-aminoethoxy)ethoxy]acetic acid Y 1 O-phosphonoTyr C 37 cysteinamide dapaconazolum dapaconazole 1-[rac-2-(2,4-dichlorophenyl)- 2-{[4-(trifluoromethyl)phenyl]methoxy}ethyl]-1H-imidazole dapaconazole 1-[rac-2-(2,4-dichlorophényl)- 2-{[4-(trifluorométhyl)phényl]méthoxy}éthyl]-1H-imidazole dapaconazol 1-[rac-2-(2,4-diclorofenil)- 2-{[4-(trifluorometil)fenil]metoxi}etil]-1H-imidazol WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 75 C19H15Cl2F3N2O N N O H F3C Cl Cl and enantiomer et énantiomère y enantiómero defactinibum defactinib N-methyl-4-({4-({[3-(N-methylmethanesulfonamido)pyrazin- 2-yl]methyl}amino)-5-(trifluoromethyl)pyrimidin- 2-yl}amino)benzamide défactinib N-méthyl-4-({4-({[3-(N-méthylméthanesulfonamido)pyrazin- 2-yl]méthyl}amino)-5-(trifluorométhyl)pyrimidin- 2-yl}amino)benzamide defactinib N-metil-4-({4-({[3-(N-metilmetanesulfonamido)pirazin- 2-il]metil}amino)-5-(trifluorometil)pirimidin- 2-il}amino)benzamida C20H21F3N8O3S N N N H HN F3C N H CH3 O N N N S CH3 CH3 OO denintuzumabum mafodotinum # denintuzumab mafodotin immunoglobulin G1-kappa auristatin F conjugate, anti- [Homo sapiens CD19 (B lymphocyte surface antigen B4, Leu-12)], humanized monoclonal antibody; gamma1 heavy chain (1-450) [humanized VH (Homo sapiens IGHV4-31*02 (84.80%) -(IGHD)-IGHJ4*01) [10.7.12] (1-120) -Homo sapiens IGHG1*01 (CH1 (121- 218), hinge (219-233), CH2 (234-343), CH3 (344-448), CHS (449-450)) (121-450)], (223-213')-disulfide with kappa light chain (1’-213’) [humanized V-KAPPA (Homo sapiens IGKV3-11*01 (85.30%) -IGKJ2*02) [5.3.9] (1'-106') -Homo sapiens IGKC*01 (107'-213')]; dimer (229-229":232-232")- bisdisulfide; conjugated, on an average of 4 cysteinyl, to monomethylauristatin F (MMAF), via a noncleavable maleimidocaproyl (mc) linker For the mafodotin part, please refer to the document "INN for pharmaceutical substances: Names for radicals, groups and others"*. Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 76 dénintuzumab mafodotine immunoglobuline G1-kappa conjuguée à l’auristatine F, anti-[Homo sapiens CD19 (antigène de surface B4 des lymphocytes B, Leu-12)], anticorps monoclonal humanisé; chaîne lourde gamma1 (1-450) [VH humanisé (Homo sapiens IGHV4-31*02 (84.80%) -(IGHD)-IGHJ4*01) [10.7.12] (1-120) -Homo sapiens IGHG1*01 (CH1 (121- 218), charnière (219-233), CH2 (234-343), CH3 (344-448), CHS (449-450)) (121-450)], (223-213')-disulfure avec la chaîne légère kappa (1’-213’) [V-KAPPA humanisé (Homo sapiens IGKV3-11*01 (85.30%) -IGKJ2*02) [5.3.9] (1'-106') -Homo sapiens IGKC*01 (107'-213')]; dimère (229- 229":232-232")-bisdisulfure; conjugué, sur 4 cystéinyl en moyenne, au monométhylauristatine F (MMAF), via un linker maléimidocaproyl (mc) non clivable Pour la partie mafodotine, veuillez-vous référer au document "INN for pharmaceutical substances: Names for radicals, groups and others"*. denintuzumab mafodotina inmunoglobulina G1-kappa conjugada con la auristatina F, anti-[CD19 de Homo sapiens (antígeno de superficie B4 de los linfocitos B, Leu-12)], anticuerpo monoclonal humanizado; cadena pesada gamma1 (1-450) [VH humanizado (Homo sapiens IGHV4-31*02 (84.80%) -(IGHD)-IGHJ4*01) [10.7.12] (1-120) -Homo sapiens IGHG1*01 (CH1 (121- 218), bisagra (219-233), CH2 (234-343), CH3 (344-448), CHS (449-450)) (121-450)], (223-213')-disulfuro con la cadena ligera kappa (1’-213’) [V-KAPPA humanizado (Homo sapiens IGKV3-11*01 (85.30%) -IGKJ2*02) [5.3.9] (1'-106') -Homo sapiens IGKC*01 (107'-213')]; dímero (229-229":232-232")-bisdisulfuro; conjugado, en 4 restos cisteinil por término medio, con monometilauristatina F (MMAF), mediante un conector maleimidocaproil (mc) no escindible La fracción mafodotina, pueden encontrarla en el documento "INN for pharmaceutical substances: Names for radicals, groups and others"*. Heavy chain / Chaîne lourde / Cadena pesadaQVQLQESGPG LVKPSQTLSL TCTVSGGSIS TSGMGVGWIR QHPGKGLEWI 50 GHIWWDDDKR YNPALKSRVT ISVDTSKNQF SLKLSSVTAA DTAVYYCARM 100 ELWSYYFDYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK 150 DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT 200 YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP 250 KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 300 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ 350 VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV 400 LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK 450 Light chain / Chaîne légère / Cadena ligera EIVLTQSPAT LSLSPGERAT LSCSASSSVS YMHWYQQKPG QAPRLLIYDT 50 SKLASGIPAR FSGSGSGTDF TLTISSLEPE DVAVYYCFQG SVYPFTFGQG 100 TKLEIKRTVA APSVFIFPPS DEQLKSGTAS VVCLLNNFYP REAKVQWKVD 150 NALQSGNSQE SVTEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL 200 SSPVTKSFNR GEC 213 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-97 147-203 264-324 370-428 22''-97'' 147''-203'' 264''-324'' 370''-428'' Intra-L (C23-C104) 23'-87' 133'-193' 23'''-87''' 133'''-193''' Inter-H-L (h 5-CL 126) * 223-213' 223''-213''' Inter-H-H (h 11, h 14) * 229-229'' 232-232'' *Two inter-chain disulfide bridges are not present on average, the antibody being conjugated to an average of 4 drug linkers, each bound to a cysteinyl via a thioether bond *Deux des ponts disulfure inter-chaines ne sont pas présents en moyenne, l'anticorps étant conjugué à une moyenne de 4 linker-principe actif, chacun via une liaison thioéther. * Faltan dos puentes disulfuro intercatenarios por estar el anticuerpo conjugado, con sendos enlaces tioéter, a una media de 4 conectores de principio activo. N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 300, 300'' WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 77 dianhydrogalactitolum dianhydrogalactitol meso-(1R,2S)-1-[(2R)-oxiran-2-yl]-2-[(2S)-oxiran- 2-yl]ethane-1,2-diol dianhydrogalactitol méso-(1R,2S)-1-[(2R)-oxiran-2-yl]-2-[(2S)-oxiran- 2-yl]éthane-1,2-diol dianhidrogalactitol meso-(1R,2S)-1-[(2R)-oxiran-2-il]-2-[(2S)-oxiran-2-il]etano- 1,2-diol C6H10O4 OHH HO H H H O O diclofenaci etalhyaluronas diclofenac etalhyaluronate hyaluronic acid partly amidified with 2-(2-{2-[(2,6- dichlorophenyl)amino]phenyl}acetyloxy)ethanamine étalhyaluronate de diclofénac acide hyaluronique partiellement amidifié par la 2-(2-{2- [(2,6-dichlorophényl)amino]phényl}acétyloxy)éthanamine etalhialuronato de diclofenaco ácido hialurónico parcialmente amidificado por 2-(2-{2- [(2,6-diclorofenil)amino]fenil}acetiloxi)etanamina [(C30H35Cl2N3O12)a(C14H21NO11)b]nH2O O OHO NH OH O OH HO2C HO OH O O OHO NH O OHHO O O CH3 HN O O CH3 H a b n HO O O HN Cl Cl diridavumabum # diridavumab immunoglobulin G1-lambda2, anti-[influenza A virus hemagglutinin HA2 subunit (H1, H2, H5, H6, H8 and H9 subtypes)], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-450) [Homo sapiens VH (IGHV1- 69*01 (84.70%) -(IGHD)-IGHJ6*03) [8.8.14](1-121) - IGHG1*03 (CH1 (122-219), hinge (220-234), CH2 (235- 344), CH3 (345-449), CHS K2>del (450)(122-450)],(224- 216')-disulfide with lambda2 light chain(1'-217') [Homo sapiens V-LAMBDA (IGLV1-51*01 (92.90%) -IGLJ2*01) [8.3.12] (1'-111') -IGLC2*01 (112'-217')]; dimer (230- 230'':233-233'')-bisdisulfide Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 78 diridavumab immunoglobuline G1-lambda2, anti-[sous-unité HA2 de l'hémagglutinine du virus de la grippe A (sous-types H1, H2, H5, H6, H8 et H9)], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-450) [Homo sapiens VH (IGHV1-69*01 (84.70%) -(IGHD)-IGHJ6*03) [8.8.14](1- 121) -IGHG1*03 (CH1 (122-219), charnière (220-234), CH2 (235-344), CH3 (345-449), CHS K2>del (450)(122- 450)],(224-216')-disulfure avec la chaîne légère lambda2 (1'-217') [Homo sapiens V-LAMBDA (IGLV1-51*01 (92.90%) -IGLJ2*01) [8.3.12] (1'-111') -IGLC2*01 (112'- 217')]; dimère (230-230'':233-233'')-bisdisulfure diridavumab inmunoglobulina G1-lambda2, anti-[subunidad HA2 de la hemaglutinina del virus de la gripe A (sub-tipos H1, H2, H5, H6, H8 y H9)], anticuerpo monoclonal de Homo sapiens ; cadena pesada gamma1 (1-450) [Homo sapiens VH (IGHV1-69*01 (84.70%) -(IGHD)-IGHJ6*03) [8.8.14] (1- 121) -IGHG1*03 (CH1 (122-219), bisagra (220-234), CH2 (235-344), CH3 (345-449), CHS K2>del (450) (122-450)], (224-216')-disulfuro con la cadena ligera lambda2 (1'-217') [Homo sapiens V-LAMBDA (IGLV1-51*01 (92.90%) - IGLJ2*01) [8.3.12] (1'-111') -IGLC2*01 (112'-217')]; dímero (230-230'':233-233'')-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEVQLVESGAE VKKPGSSVKV SCKASGGPFR SYAISWVRQA PGQGPEWMGG 50 IIPIFGTTKY APKFQGRVTI TADDFAGTVY MELSSLRSED TAMYYCAKHM 100 GYQVRETMDV WGKGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV 150 KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ 200 TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG GPSVFLFPPK 250 PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP 350 QVYTLPPSRE EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 400 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG 450 Light chain / Chaîne légère / Cadena ligera QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NDYVSWYQQL PGTAPKLLIY 50 DNNKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEANYYCA TWDRRPTAYV 100 VFGGGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT 150 VAWKADSSPV KAGVETTTPS KQSNNKYAAS SYLSLTPEQW KSHRSYSCQV 200 THEGSTVEKT VAPTECS 217 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 148-204 265-325 371-429 22''-96'' 148''-204'' 265''-325'' 371''-429'' Intra-L (C23-C104) 22'-89' 139'-198' 22'''-89''' 139'''-198''' Inter-H-L (h 5-CL 126) 224-216' 224''-216''' Inter-H-H (h 11, h 14) 230-230'' 233-233'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 301, 301'' Other post-translational modifications Autres modifications post-traductionnelles Otras modificaciones post-traduccionales Lacking H chain C-terminal lysine (CHS K2>del) eflapegrastimum # eflapegrastim human granulocyte colony-stimulating factor and human IgG4 Fc dimer linked together with polyethylene glycol derivative, produced in Escherichia coli: Nα.1,N1.9'-[ω-(oxypropane-1,3-diyl)-α-(propane- 1,3-diyl)poly(oxyethylene)] des-(1-L-alanine,37-39)- [18-L-serine(C>S),69-L-serine(P>S)]human granulocyte colony-stimulating factor (G-CSF, pluripoietin) (1-174)- peptide and des-(1-8)-human immunoglobulin G4 Fc fragment (IGHG4*01 H-CH2-CH3) (9'-229')-peptide dimer (11'-11'')-disulfide WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 79 éflapégrastim le facteur de stimulation de colonies de granulocytes humain et le dimère du fragment Fc de l’IgG4 humaine, produits par Escherichia coli, reliés par un radical substituant dérivé du polyéthylèneglycol: Nα.1,N1.9'-[ω-(oxypropane-1,3-diyl)-α-(propane- 1,3-diyl)poly(oxyethylene)] dès-(1-L-alanine,37-39)- [18-L-sérine(C>S), 69-L-sérine(P>S)]facteur de stimulation de colonies de granulocytes humain (G-CSF, pluripoiétine) (1-174)-peptide et (11'-11'')-disulfure du dimère de dès-(1-8)-fragment Fc de l’immunoglobuline G4 humaine (IGHG4*01 H-CH2-CH3) (9'-229')-peptide eflapegrastim producto de la unión, mediante un radical derivado del polietilenglicol, del factor estimulante de colonias de granulocitos humano y el dímero del fragmento Fc de la IgG4 humana, producidos por Escherichia coli. Nα.1,N1.9'-[ω-(oxipropano-1,3-diil)-α-(propano- 1,3-diil)poli(oxietileno)] des-(1-L-alanina,37-39)- [18-L-serina(C>S),69-L-serina(P>S)]]factor estimulante de colonias de granulocitos humano (G-CSF, pluripoyetina) (1-174)-péptido y (11'-11'')-disulfuro del dímero de des-(1-8)-fragmento Fc de la inmunoglobulina G4 humana (IGHG4*01 H-CH2-CH3) (9'-229')-péptido O N H ON H CO2H CH3 HO H CO2H H n P - T 9' - 1 Human G-CSF derivative sequence / Séquence dérivée du G-CSF humain / Secuencia derivada de G-CSF humano TPLGPASSLP QSFLLKSLEQ VRKIQGDGAA LQEKLCATYK LCHPEELVLL 50 GHSLGIPWAP LSSCSSQALQ LAGCLSQLHS GLFLYQGLLQ ALEGISPELG 100 PTLDTLQLDV ADFATTIWQQ MEELGMAPAL QPTQGAMPAF ASAFQRRAGG 150 VLVASHLQSF LEVSYRVLRH LAQP 174 hIGHG4 Fc monomer / Monomère du Fc de hIGHG4 / Monómero de Fc de hIGHG4 PS CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ 50' EDPEVQFNWY VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE 100' YKCKVSNKGL PSSIEKTISK AKGQPREPQV YTLPPSQEEM TKNQVSLTCL 150' VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ 200' EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229' hIGHG4 Fc monomer / Monomère du Fc de hIGHG4 / Monómero de Fc de hIGHG4 PS CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ 50'' EDPEVQFNWY VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE 100'' YKCKVSNKGL PSSIEKTISK AKGQPREPQV YTLPPSQEEM TKNQVSLTCL 150'' VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ 200'' EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229'' Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 11'-11'' 36-42 43'-103' 43''-103'' 64-74 149'-207' 149''-207'' Modified residues / Résidus modifiés / Restos modificados efmoroctocogum alfa # efmoroctocog alfa recombinant DNA derived (1-742)-(1637-2332)-human blood coagulation factor VIII fusion protein with immunoglobulin G1 Fc domain fragment, produced in HEK293H cells, glycoform alfa: des-(743-1636)-human blood coagulation factor VIII (antihemophilic factor, procoagulant component) fusion protein with human immunoglobulin G1 Fc fragment (IGHG1*01 H-CH2-CH3)-(6-231)-peptide (1444-6':1447- 9')-bisdisulfide with human immunoglobulin G1 Fc fragment (IGHG1*01 H-CH2-CH3)-(6-231)-peptide Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 80 efmoroctocog alfa (1-742)-(1637-2332)-facteur VIII de coagulation humain protéine de fusion avec le fragment Fc de l’immunoglobuline G1, produite dans les cellules HEK293H à partir d’ADN recombinant, forme glycosylée alfa: dès-(743-1636)-facteur VIII de coagulation humain (facteur antihémophilique, composé procoagulant) protéine de fusion avec le fragment Fc de l’immunoglobuline G1 humaine (IGHG1*01 H-CH2-CH3)-(6-231)-peptide (1444- 6':1447-9')-bisdisulfure avec le fragment Fc de l’immunoglobuline G1 humaine (IGHG1*01 H-CH2-CH3)- (6-231)-peptide efmoroctocog alfa (1-742)-(1637-2332)-factor VIII de coagulación humano proteína de fusión con el fragmento Fc de la inmunoglobulina G1, producida en las células HEK293H a partir de ADN recombinante, forma glicosilada alfa: des-(743-1636)-factor VIII de coagulación humano (factor antihemofílico, componente procoagulante) proteína de fusión con el fragmento Fc de la inmunoglobulina G1 humana (IGHG1*01 H-CH2-CH3)-(6-231)-péptido (1444- 6':1447-9')-bisdisulfuro con el fragmento Fc de la inmunoglobulina G1 humana (IGHG1*01 H-CH2-CH3)-(6- 231)-péptido CO2H NH2H O S HO O O Glycosylation sites (N) / Sites de glycosylation (N) / Posiciones de glicosilación (N) Asn-41 Asn-77' Asn-239 Asn-916 Asn-1224 Asn-1515 Y 346, 718, 719, 723, 770, 786 O-sulfoTyr Fusion protein / Protéine de fusion / Proteína de fusión ATRRYYLGAV ELSWDYMQSD LGELPVDARF PPRVPKSFPF NTSVVYKKTL 50 FVEFTDHLFN IAKPRPPWMG LLGPTIQAEV YDTVVITLKN MASHPVSLHA 100 VGVSYWKASE GAEYDDQTSQ REKEDDKVFP GGSHTYVWQV LKENGPMASD 150 PLCLTYSYLS HVDLVKDLNS GLIGALLVCR EGSLAKEKTQ TLHKFILLFA 200 VFDEGKSWHS ETKNSLMQDR DAASARAWPK MHTVNGYVNR SLPGLIGCHR 250 KSVYWHVIGM GTTPEVHSIF LEGHTFLVRN HRQASLEISP ITFLTAQTLL 300 MDLGQFLLFC HISSHQHDGM EAYVKVDSCP EEPQLRMKNN EEAEDYDDDL 350 TDSEMDVVRF DDDNSPSFIQ IRSVAKKHPK TWVHYIAAEE EDWDYAPLVL 400 APDDRSYKSQ YLNNGPQRIG RKYKKVRFMA YTDETFKTRE AIQHESGILG 450 PLLYGEVGDT LLIIFKNQAS RPYNIYPHGI TDVRPLYSRR LPKGVKHLKD 500 FPILPGEIFK YKWTVTVEDG PTKSDPRCLT RYYSSFVNME RDLASGLIGP 550 LLICYKESVD QRGNQIMSDK RNVILFSVFD ENRSWYLTEN IQRFLPNPAG 600 VQLEDPEFQA SNIMHSINGY VFDSLQLSVC LHEVAYWYIL SIGAQTDFLS 650 VFFSGYTFKH KMVYEDTLTL FPFSGETVFM SMENPGLWIL GCHNSDFRNR 700 GMTALLKVSS CDKNTGDYYE DSYEDISAYL LSKNNAIEPR SFSQNPPVLK 750 RHQREITRTT LQSDQEEIDY DDTISVEMKK EDFDIYDEDE NQSPRSFQKK 800 TRHYFIAAVE RLWDYGMSSS PHVLRNRAQS GSVPQFKKVV FQEFTDGSFT 850 QPLYRGELNE HLGLLGPYIR AEVEDNIMVT FRNQASRPYS FYSSLISYEE 900 DQRQGAEPRK NFVKPNETKT YFWKVQHHMA PTKDEFDCKA WAYFSDVDLE 950 KDVHSGLIGP LLVCHTNTLN PAHGRQVTVQ EFALFFTIFD ETKSWYFTEN 1000 MERNCRAPCN IQMEDPTFKE NYRFHAINGY IMDTLPGLVM AQDQRIRWYL 1050 LSMGSNENIH SIHFSGHVFT VRKKEEYKMA LYNLYPGVFE TVEMLPSKAG 1100 IWRVECLIGE HLHAGMSTLF LVYSNKCQTP LGMASGHIRD FQITASGQYG 1150 QWAPKLARLH YSGSINAWST KEPFSWIKVD LLAPMIIHGI KTQGARQKFS 1200 SLYISQFIIM YSLDGKKWQT YRGNSTGTLM VFFGNVDSSG IKHNIFNPPI 1250 IARYIRLHPT HYSIRSTLRM ELMGCDLNSC SMPLGMESKA ISDAQITASS 1300 YFTNMFATWS PSKARLHLQG RSNAWRPQVN NPKEWLQVDF QKTMKVTGVT 1350 TQGVKSLLTS MYVKEFLISS SQDGHQWTLF FQNGKVKVFQ GNQDSFTPVV 1400 NSLDPPLLTR YLRIHPQSWV HQIALRMEVL GCEAQDLYDK THTCPPCPAP 1450 ELLGGPSVFL FPPKPKDTLM ISRTPEVTCV VVDVSHEDPE VKFNWYVDGV 1500 EVHNAKTKPR EEQYNSTYRV VSVLTVLHQD WLNGKEYKCK VSNKALPAPI 1550 EKTISKAKGQ PREPQVYTLP PSRDELTKNQ VSLTCLVKGF YPSDIAVEWE 1600 SNGQPENNYK TTPPVLDSDG SFFLYSKLTV DKSRWQQGNV FSCSVMHEAL 1650 HNHYTQKSLS LSPG 1664 Immunoglobulin Fc fragment / fragment Fc d'immunoglobuline / fragmento Fc de inmunoglobulina DKTHTCPPCP APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED 50' PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH QDWLNGKEYK 100' CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSRDELTK NQVSLTCLVK 150' GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG 200' NVFSCSVMHE ALHNHYTQKS LSLSPG 226' Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 6'-1444 9'-1447 41'-101' 147'-205' 153-179 248-329 528-554 630-711 938-964 1005-1009 1127-1275 1280-1432 1479-1539 1585-1643 Modified residues / Résidus modifiés / Restos modificados WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 81 efpeglenatidum # efpeglenatide exenatide derivative and human IgG4 Fc dimer linked together with polyethylene glycol derivative: N6.27,N1.9'-[ω-(oxypropane-1,3-diyl)-α-(propane- 1,3-diyl)poly(oxyethylene)] [1-(imidazol-4-ylacetic acid)]exendin-4 Heloderma suspectum (Gila monster), human immunoglobulin G4 Fc fragment-(9'-229')-peptide dimer (11'-11'')-disulfide efpèglénatide dérivé de l’exénatide et du dimère de l’IgG4 Fc liés par un pont dérivé du polyéthylèneglycol : N6.27,N1.9'-[ω-(oxypropane-1,3-diyl)-α-(propane- 1,3-diyl)poly(oxyéthylène)] [1-acide (imidazol- 4-yl)acétique]exendine-4 Heloderma suspectum (monstre de Gila), fragment Fc de l’immunoglobuline G4 humaine- (9'-229')-peptide (11'-11'')-disulfure du dimère efpeglenatida derivado de la exenatida y del dímero de la IgG4 Fc unidos por un puente derivado del polietilenglicol : N6.27,N1.9'-[ω-(oxipropano-1,3-diil)-α-(propano- 1,3-diil)poli(oxitileno)] [1-ácido (imidazol- 4-il)acético]exendina-4 Heloderma suspectum (monstruo de Gila), fragmento Fc de la inmunoglobulina G4 humana- (9'-229')-péptido (11'-11'')-disulfuro del dímero H2N CO2H n H N CO2H H O O HN H2N H NH2 O OH CO2H N HN H 1 (imidazol-4-yl)acetic acid S 39 serinamide P - K 9' - 27 Modified exendin-4 / Exendine-4 modifiée / Exendina-4 modificada HGEGTFTSDL SKQMEEEAVR LFIEWLKNGG PSSGAPPPS 39 hIGHG4 Fc monomer / Monomère du Fc de hIGHG4 / Monómero del Fc de hIGHG4 PS CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ 50' EDPEVQFNWY VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE 100' YKCKVSNKGL PSSIEKTISK AKGQPREPQV YTLPPSQEEM TKNQVSLTCL 150' VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ 200' EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229' hIGHG4 Fc monomer / Monomère du Fc de hIGHG4 / Monómero del Fc de hIGHG4 PS CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ 50'' EDPEVQFNWY VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE 100'' YKCKVSNKGL PSSIEKTISK AKGQPREPQV YTLPPSQEEM TKNQVSLTCL 150'' VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ 200'' EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229'' Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 11'-11'' 43'-103' 43''-103'' 149'-207' 149''-207'' Modified residues / Résidus modifiés / Restos modificados emactuzumabum # emactuzumab immunoglobulin G1-kappa, anti-[Homo sapiens CSF1R (colony stimulating factor 1 receptor, CSF-1R, CSF-1-R, macrophage colony-stimulating factor 1 receptor, c-fms, FMS, CD115)], humanized monoclonal antibody; gamma1 heavy chain (1-446) [humanized VH (Homo sapiens IGHV1-18*01 (92.90%) -(IGHD)-IGHJ6*01) [8.7.10] (1-116) -Homo sapiens IGHG1*01 (CH1 (117- 214), hinge (215-229), CH2 (230-339), CH3 (340-444), CHS (445-446)) (117-446)], (219-213')-disulfide with kappa light chain (1’-213’) [humanized V-KAPPA (Homo sapiens IGKV1-39*01 (86.30%) -IGKJ2*01) [6.3.8] (1'-106') -Homo sapiens IGKC*01 (107'-213')]; dimer (225-225":228-228")- bisdisulfide Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 82 émactuzumab immunoglobuline G1-kappa, anti-[Homo sapiens CSF1R (récepteur du facteur 1 stimulant de colonies, CSF-1R, CSF-1-R, récepteur du facteur 1 stimulant des colonies de macrophages, c-fms, FMS, CD115)], anticorps monoclonal humanisé; chaîne lourde gamma1 (1-446) [VH humanisé (Homo sapiensIGHV1-18*01 (92.90%) -(IGHD)-IGHJ6*01) [8.7.10] (1- 116) -Homo sapiens IGHG1*01 (CH1 (117-214), charnière (215-229), CH2 (230-339), CH3 (340-444), CHS (445-446)) (117-446)],(219-213')-disulfure avec la chaîne légère kappa (1’-213’) [V-KAPPA humanisé (Homo sapiens IGKV1-39*01 (86.30%) -IGKJ2*01) [6.3.8] (1'-106') -Homo sapiens IGKC*01 (107'-213')]; dimère (225-225":228-228")-bisdisulfure emactuzumab inmunoglobulina G1-kappa, anti-[Homo sapiens CSF1R (receptor del factor 1 estimulante de colonias, CSF-1R, CSF-1-R, receptor del factor 1 estimulante de colonias de macrófagos, c-fms, FMS, CD115)], anticuerpo monoclonal humanizado; cadena pesada gamma1 (1-446) [VH humanizado (Homo sapiens IGHV1-18*01 (92.90%) -(IGHD)-IGHJ6*01) [8.7.10] (1- 116) -Homo sapiens IGHG1*01 (CH1 (117-214), bisagra (215- 229), CH2 (230-339), CH3 (340-444), CHS (445-446)) (117- 446)], (219-213')-disulfuro con la cadena ligera kappa (1’-213’) [V-KAPPA humanizado (Homo sapiens IGKV1-39*01 (86.30%) -IGKJ2*01) [6.3.8] (1'-106') -Homo sapiens IGKC*01 (107'- 213')]; dímero (225-225":228-228")-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKASGYTFT SYDISWVRQA PGQGLEWMGV 50 IWTDGGTNYA QKLQGRVTMT TDTSTSTAYM ELRSLRSDDT AVYYCARDQR 100 LYFDVWGQGT TVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP 150 EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN 200 VNHKPSNTKV DKKVEPKSCD KTHTCPPCPA PELLGGPSVF LFPPKPKDTL 250 MISRTPEVTC VVVDVSHEDP EVKFNWYVDG VEVHNAKTKP REEQYNSTYR 300 VVSVLTVLHQ DWLNGKEYKC KVSNKALPAP IEKTISKAKG QPREPQVYTL 350 PPSRDELTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY KTTPPVLDSD 400 GSFFLYSKLT VDKSRWQQGN VFSCSVMHEA LHNHYTQKSL SLSPGK 446 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCRASEDVN TYVSWYQQKP GKAPKLLIYA 50 ASNRYTGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SFSYPTFGQG 100 TKLEIKRTVA APSVFIFPPS DEQLKSGTAS VVCLLNNFYP REAKVQWKVD 150 NALQSGNSQE SVTEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL 200 SSPVTKSFNR GEC 213 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-95 143-199 260-320 366-424 22''-95'' 143''-199'' 260''-320'' 366''-424'' Intra-L (C23-C104) 23'-88' 133'-193' 23'''-88''' 133'''-193''' Inter-H-L (h 5-CL 126) 219-213' 219''-213''' Inter-H-H (h 11, h 14) 225-225'' 228-228'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 296, 296'' emibetuzumabum # emibetuzumab immunoglobulin G4-kappa, anti-[Homo sapiens MET (met proto-oncogene, hepatocyte growth factor receptor, HGFR, scatter factor receptor, HGF/SF receptor, receptor tyrosine- protein kinase c-Met, papillary renal cell carcinoma 2, RCCP2)], humanized monoclonal antibody; gamma4 heavy chain (1-441) [humanized VH (Homo sapiens IGHV1-2*02 (87.80%) -(IGHD)-IGHJ5*01 L123>T (110) (1- 115)), IGHG4*01 (CH1 (116-213), hinge S10>P (223) (214- 225), CH2 F1.3>A (229), L1.2>A (230) (226-335), CH3 (336- 440), CHS K2>del (441)) (116-441)],(129-215')-disulfide with kappa light chain (1’-215’) [humanized V-KAPPA (Homo sapiens IGKV1-39*01 (84.40%) -IGKJ4*01) [7.3.9] (1'-108') - Homo sapiens IGKC*01 (109'-215')]; dimer (221-221":224- 224")-bisdisulfide WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 83 émibétuzumab immunoglobuline G4-kappa, anti-[Homo sapiens MET (proto-oncogène met, récepteur du facteur de croissance hépatocytaire, HGFR, récepteur du facteur de dispersion, récepteur de l'HGF/SF, récepteur protéine-tyrosine kinase c-Met, carcinome papillaire à cellules rénales 2, RCCP2)], anticorps monoclonal humanisé; chaîne lourde gamma4 (1-441) [VH humanisé (Homo sapiens IGHV1-2*02 (87.80%) -(IGHD)-IGHJ5*01 L123>T (110) (1-115)), IGHG4*01 (CH1 (116-213), charnière S10>P (223) (214-225), CH2 F1.3>A (229), L1.2>A (230) (226-335), CH3 (336-440), CHS K2>del (441)) (116-441)], (129-215')-disulfure avec la chaîne légère kappa (1’-215’) [V-KAPPA humanisé (Homo sapiens IGKV1-39*01 (84.40%) -IGKJ4*01) [7.3.9] (1'-108') -Homo sapiens IGKC*01 (109'-215')]; dimère (221-221":224-224")- bisdisulfure emibetuzumab inmunoglobulina G4-kappa, anti-[Homo sapiens MET (proto-oncogén met, receptor del factor de crecimiento de hepatocitos, HGFR, receptor del factor de dispersión, receptor del HGF/SF, receptor proteína-tirosina kinasa c- Met, carcinoma papilar de células renales 2, RCCP2)], anticuerpo monoclonal humanizado; cadena pesada gamma4 (1-441) [VH humanizada (Homo sapiens IGHV1-2*02 (87.80%) -(IGHD)-IGHJ5*01 L123>T (110) (1-115)) , IGHG4*01 (CH1 (116-213), bisagra S10>P (223) (214-225), CH2 F1.3>A (229), L1.2>A (230) (226- 335), CH3 (336-440), CHS K2>del (441)) (116-441)], (129- 215')-disulfuro con la cadena ligera kappa (1’-215’) [V- KAPPA humanizado (Homo sapiens IGKV1-39*01 (84.40%) -IGKJ4*01) [7.3.9] (1'-108')-Homo sapiens IGKC*01 (109'-215')]; dímero (221-221":224-224")- bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKASGYTFT DYYMHWVRQA PGQGLEWMGR 50 VNPNRRGTTY NQKFEGRVTM TTDTSTSTAY MELRSLRSDD TAVYYCARAN 100 WLDYWGQGTT VTVSSASTKG PSVFPLAPCS RSTSESTAAL GCLVKDYFPE 150 PVTVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTKTYTCNV 200 DHKPSNTKVD KRVESKYGPP CPPCPAPEAA GGPSVFLFPP KPKDTLMISR 250 TPEVTCVVVD VSQEDPEVQF NWYVDGVEVH NAKTKPREEQ FNSTYRVVSV 300 LTVLHQDWLN GKEYKCKVSN KGLPSSIEKT ISKAKGQPRE PQVYTLPPSQ 350 EEMTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP PVLDSDGSFF 400 LYSRLTVDKS RWQEGNVFSC SVMHEALHNH YTQKSLSLSL G 441 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCSVSSSVS SIYLHWYQQK PGKAPKLLIY 50 STSNLASGVP SRFSGSGSGT DFTLTISSLQ PEDFATYYCQ VYSGYPLTFG 100 GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 142-198 256-316 362-420 22''-96'' 142''-198'' 256''-316'' 362''-420'' Intra-L (C23-C104) 23'-89' 135'-195' 23'''-89''' 135'''-195''' Inter-H-L (CH1 10-CL 126) 129-215' 129''-215''' Inter-H-H (h 8, h 11) 221-221'' 224-224'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 292, 292'' Other post-translational modifications Autres modifications post-traductionnelles Otras modificaciones post-traduccionales Lacking H chain C-terminal lysine (CHS K2>del) Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 84 enadenotucirevum # enadenotucirev chimeric oncolytic adenovirus Ad3/Ad11p containing two deletions in the viral genome in the E3 region (2444 bp) and in the E4 region (24 bp) and 197 non-homologous nucleotides in the E2B region énadénotucirev adénovirus chimérique oncolytique Ad3/Ad11p contenant deux suppressions dans le génome viral, dans la région E3 (2444 pb) et dans la région E4 (24 pb) et 197 nucléotides non-homologues dans la région E2B enadenotucirev adenovirus quimérico oncolítico Ad3/Ad11p que contiene dos delecciones en el genoma viral, en la región E3 (2444 pb) y en la región E4 (24 pb) y 197 nucléotidos no-homólogos en la región E2B enceniclinum encenicline N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-chloro- 1-benzothiophene-2-carboxamide encénicline N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-chloro- 1-benzothiophène-2-carboxamide enceniclina N-[(3R)-1-azabiciclo[2.2.2]octan-3-il]-7-cloro- 1-benzotiofeno-2-carboxamida C16H17ClN2OS N N H O S Cl H esuberaprostum esuberaprost (+)-4-{(1R,2R,3aS,8bS)-2-hydroxy-1-[(1E,3S,4S)-3- hydroxy-4-methyloct-1-en-6-yn-1-yl]-2,3,3a,8b-tetrahydro- 1H-cyclopenta[b][1]benzofuran-5-yl}butanoic acid ésubéraprost (+)-acide4-{(1R,2R,3aS,8bS)-2-hydroxy-1-[(1E,3S,4S)-3- hydroxy-4-méthyloct-1-én-6-yn-1-yl]-2,3,3a,8b-tétrahydro- 1H-cyclopenta[b][1]benzofuran-5-yl}butanoïque esuberaprost (+)-ácido 4-{(1R,2R,3aS,8bS)-2-hidroxi-1-[(1E,3S,4S)-3- hidroxi-4-metiloct-1-en-6-in-1-il]-2,3,3a,8b-tetrahidro- 1H-ciclopenta[b][1]benzofuran-5-il}butanoico WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 85 C24H30O5 O HO H H CH3 CO2H HO H H H H3C H evofosfamidum evofosfamide (1-methyl-2-nitro-1H-imidazol-5-yl)methyl N,N'-bis(2- bromoethyl)phosphorodiamidate évofosfamide N,N'-bis(2-bromoéthyl)phosphorodiamidate de (1-méthyl- 2-nitro-1H-imidazol-5-yl)méthyle evofosfamida N,N'-bis(2-bromoetil)fosforodiamidato de (1-metil-2-nitro- 1H-imidazol-5-il)metilo C9H16Br2N5O4P O P O HN HN Br Br N N CH3O2N ferricum maltolum ferric maltol tris(2-methyl-4-oxo-κO-4H-pyran-3-olato-κO)iron(III) maltol ferrique tris(2-méthyl-4-oxo-κO-4H-pyran-3-olato-κO)fer(III) maltol férrico tris(2-metil-4-oxo-κO-4H-piran-3-olato-κO)hierro(III) C18H15FeO9 O CH3 O O O CH3O O OH3C O O Fe filociclovirum filociclovir 2-amino-9-{(Z)-[2,2- bis(hydroxymethyl)cyclopropylidene]methyl}-1,9-dihydro- 6H-purin-6-one Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 86 filociclovir 2-amino-9-{(Z)-[2,2- bis(hydroxyméthyl)cyclopropylidène]méthyl}-1,9-dihydro- 6H-purin-6-one filociclovir 2-amino-9-{(Z)-[2,2-bis(hidroximetil)ciclopropilideno]metil}- 1,9-dihidro-6H-purin-6-ona C11H13N5O3 HN N N N H2N O OH OH firivumabum # firivumab immunoglobulin G1-kappa, anti-[influenza A virus hemagglutinin HA], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-453) [Homo sapiens VH (IGHV1- 69*01 (86.70%) -(IGHD)-IGHJ5*02) [8.8.16] (1-123) - IGHG1*03 (CH1 (124-221), hinge (222-236), CH2 (237- 346), CH3 E12>D (362), M14>L (364), A110>G (437) (347-451), CHS (452-453)) (124-453)], (226-214')-disulfide with kappa light chain (1'-214') [Homo sapiens V-KAPPA (IGKV3-15*01 (83.20%) -IGKJ3*01) [6.3.9] (1'-107') - IGKC*01 (108'-214')]; dimer (232-232'':235-235'')- bisdisulfide firivumab immunoglobuline G1-kappa, anti-[hémagglutinine HA du virus de la grippe A], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-453) [Homo sapiens VH (IGHV1-69*01 (86.70%) -(IGHD)-IGHJ5*02) [8.8.16] (1- 123) -IGHG1*03 (CH1 (124-221), charnière (222-236), CH2 (237-346), CH3 E12>D (362), M14>L (364), A110>G (437) (347-451), CHS (452-453)) (124-453)], (226-214')- disulfure avec la chaîne légère kappa (1'-214') [Homo sapiens V-KAPPA (IGKV3-15*01 (83.20%) -IGKJ3*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dimère (232- 232'':235-235'')-bisdisulfure firivumab inmunoglobulina G1-kappa, anti-[hemaglutinina HA del virus de la gripe A], anticuerpo monoclonal de Homo sapiens; cadena pesada gamma1 (1-453) [Homo sapiens VH (IGHV1-69*01 (86.70%) -(IGHD)-IGHJ5*02) [8.8.16] (1- 123) -IGHG1*03 (CH1 (124-221), bisagra (222-236), CH2 (237-346), CH3 E12>D (362), M14>L (364), A110>G (437) (347-451), CHS (452-453)) (124-453)], (226-214')-disulfuro con la cadena ligera kappa (1'-214') [Homo sapiens V-KAPPA (IGKV3-15*01 (83.20%) -IGKJ3*01) [6.3.9] (1'- 107') -IGKC*01 (108'-214')]; dímero (232-232'':235-235'')- bisdisulfuro WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 87 Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKMPGSSVKV SCKTSGVFFS SHAISWVRQA PGQGLEWMGG 50 ISPMFGTTHY AQKFQGRVTI TADQSTTTAY MELTSLTSED TAVYYCARDG 100 AGSYYPLNWF DPWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC 150 LVKDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG 200 TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL LGGPSVFLFP 250 PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300 QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR 350 EPQVYTLPPS RDELTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT 400 PPVLDSDGSF FLYSKLTVDK SRWQQGNVFS CSVMHEGLHN HYTQKSLSLS 450 PGK 453 Light chain / Chaîne légère / Cadena ligera EIVLTQSPAT LSLSPGERAT LSCRASENIW NNLAWYQQKP GQAPRLLISG 50 ASTGATGVPS RFRGSGSRTE FTLTISSLQS EDFAIYFCQQ YNSWPRTFGP 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 150-206 267-327 373-431 22''-96'' 150''-206'' 267''-327'' 373''-431'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 226-214' 226''-214''' Inter-H-H (h 11, h 14) 232-232'' 235-235'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 303, 303'' fosdagrocoratum fosdagrocorat (2R,4aS,10aR)-4a-benzyl-7-[(2-methylpyridin- 3-yl)carbamoyl]-2-(trifluoromethyl)-1,2,3,4,4a,9,10,10a- octahydrophenanthren-2-yl dihydrogen phosphate fosdagrocorat dihydrogénophosphate de (2R,4aS,10aR)-4a-benzyl- 7-[(2-méthylpyridin-3-yl)carbamoyl]-2-(trifluorométhyl)- 1,2,3,4,4a,9,10,10a-octahydrophénanthrén-2-yle fosdagrocorat dihidrógenofosfato de (2R,4aS,10aR)-4a-bencil- 7-[(2-metilpiridin-3-il)carbamoil]-2-(trifluorometil)- 1,2,3,4,4a,9,10,10a-octahidrofenantren-2-ilo C29H30F3N2O5P H N N CH3 O H CF3 O P OH OH O funapidum funapide (3'S)-1'-{[5-(trifluoromethyl)furan-2-yl]methyl}-2H,6H- spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one funapide (3'S)-1'-{[5-(trifluorométhyl)furan-2-yl]méthyl}-2H,6H- spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one funapida (3'S)-1'-{[5-(trifluorometil)furan-2-il]metil}-2H,6H- espiro[furo[2,3-f][1,3]benzodioxol-7,3'-indol]-2'(1'H)-ona Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 88 C22H14F3NO5 O N O O OF3C O furaprevirum furaprevir cyclopentyl {(2R,6S,12Z,13aS,14aR,16aS)-14a-[(1- methylcyclopropane-1-sulfonamido)carbonyl]-2-[(2-{4- [(propan-2-yl)oxy]phenyl}benzofuro[3,2-d]pyrimidin- 4-yl)oxy]-5,16-dioxo- 1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a- hexadecahydrocyclopropa[e]pyrrolo[1,2- a][1,4]diazacyclopentadecin-6-yl}carbamate furaprévir {(2R,6S,12Z,13aS,14aR,16aS)-14a-[(1- méthylcyclopropane-1-sulfonamido)carbonyl]-2-[(2-{4- [(propan-2-yl)oxy]phényl}benzofuro[3,2-d]pyrimidin- 4-yl)oxy]-5,16-dioxo- 1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a- hexadécahydrocyclopropa[e]pyrrolo[1,2- a][1,4]diazacyclopentadécin-6-yl}carbamate de cyclopentyle furaprevir {(2R,6S,12Z,13aS,14aR,16aS)-14a-[(1-metilciclopropano- 1-sulfonamido)carbonil]-2-[(2-{4-[(propan-2- il)oxi]fenil}benzofuro[3,2-d]pirimidin-4-il)oxi]-5,16-dioxo- 1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a- hexadecahidrociclopropa[e]pirrolo[1,2- a][1,4]diazaciclopentadecin-6-il}carbamato de ciclopentilo C47H56N6O10S N N H O O H H H HN H O O O O NH S O O N N O O CH3 CH3 CH3 gedatolisibum gedatolisib N-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)- N'-{4-[4,6-di(morpholin-4-yl)-1,3,5-triazin-2-yl]phenyl}urea gédatolisib N-(4-{[4-(diméthylamino)pipéridin-1-yl]carbonyl}phényl)- N'-{4-[4,6-di(morpholin-4-yl)-1,3,5-triazin-2-yl]phényl}urée WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 89 gedatolisib N-(4-{[4-(dimetilamino)piperidin-1-il]carbonil}fenil)- N'-{4-[4,6-di(morfolin-4-il)-1,3,5-triazin-2-il]fenil}urea C32H41N9O4 N N N N N N H O N H O N N CH3 CH3 O O glasdegibum glasdegib N-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin- 4-yl]-N'-(4-cyanophenyl)urea glasdégib N-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-méthylpipéridin- 4-yl]-N'-(4-cyanophényl)urée glasdegib N-[(2R,4R)-2-(1H-benzoimidazol-2-il)-1-metilpiperidin-4-il]- N'-(4-cianofenil)urea C21H22N6O N CH3 N H N H O HN N NC HH idasanutlinum idasanutlin 4-[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro- 2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine- 2-carboxamido]-3-methoxybenzoic acid idasanutline acide 4-[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophényl)- 4-(4-chloro-2-fluorophényl)-4-cyano-5-(2,2- diméthylpropyl)pyrrolidine-2-carboxamido]- 3-méthoxybenzoïque idasanutlina ácido 4-[(2R,3S,4R,5S)-3-(3-cloro-2-fluorofenil)-4-(4-cloro- 2-fluorofenil)-4-ciano-5-(2,2-dimetilpropil)pirrolidina- 2-carboxamido]-3-metoxibenzoico Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 90 C31H29Cl2F2N3O4 H N F F Cl Cl O HN CO2H OCH3 NC H CH3H3C H3C H H imalumabum # imalumab immunoglobulin G1-kappa, anti-[Homo sapiens MIF (macrophage migration inhibitory factor, glycosylation- inhibiting factor, GLIF, GIF)], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-448) [Homo sapiens VH (IGHV3- 23*01 (92.80%) -(IGHD)-IGHJ3*01) [8.8.11] (1-118) - IGHG1*03 (CH1 (119-216), hinge (217-231), CH2 (232- 341), CH3 (342-446), CHS (447-448)) (119-448)], (221- 214')-disulfide with kappa light chain (1'-214') [Homo sapiens V-KAPPA (IGKV1-39*01 (85.30%) -IGKJ4*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dimer (227- 227'':230-230'')-bisdisulfide imalumab immunoglobuline G1-kappa, anti-[Homo sapiens MIF (facteur inhibiteur de la migration des macrophages, facteur inhibant la glycosylation, GLIF, GIF)], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-448) [Homo sapiens VH (IGHV3-23*01 (92.80%) -(IGHD)-IGHJ3*01) [8.8.11] (1- 118) -IGHG1*03 (CH1 (119-216), charnière (217-231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (119- 448)], (221-214')-disulfure avec la chaîne légère kappa (1'- 214') [Homo sapiens V-KAPPA (IGKV1-39*01 (85.30%) - IGKJ4*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dimère (227-227'':230-230'')-bisdisulfure imalumab inmunoglobulina G1-kappa, anti-[Homo sapiens MIF (facteur inhibidor de la migración de macrófagos, factor inhibidor de la glicosilación, GLIF, GIF)], anticuerpo monoclonal de Homo sapiens ; cadena pesada gamma1 (1-448) [Homo sapiens VH (IGHV3-23*01 (92.80%) -(IGHD)-IGHJ3*01) [8.8.11] (1- 118) -IGHG1*03 (CH1 (119-216), bisagra (217-231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (119-448)], (221-214')-disulfuro con la cadena kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1-39*01 (85.30%) -IGKJ4*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dímero (227- 227'':230-230'')-bisdisulfuro WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 91 Heavy chain / Chaîne lourde / Cadena pesadaEVQLLESGGG LVQPGGSLRL SCAASGFTFS IYSMNWVRQA PGKGLEWVSS 50 IGSSGGTTYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAGSQ 100 WLYGMDVWGQ GTTVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY 150 FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI 200 CNVNHKPSNT KVDKRVEPKS CDKTHTCPPC PAPELLGGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNST 300 YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 350 TLPPSREEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD 400 SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK 448 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCRSSQRIM TYLNWYQQKP GKAPKLLIFV 50 ASHSQSGVPS RFRGSGSETD FTLTISGLQP EDSATYYCQQ SFWTPLTFGG 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 145-201 262-322 368-426 22''-96'' 145''-201'' 262''-322'' 368''-426'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 221-214' 221''-214''' Inter-H-H (h 11, h 14) 227-227'' 230-230'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' indoximodum indoximod 1-methyl-D-tryptophan indoximod 1-méthyl-D-tryptophane indoximod 1-metil-D-triptófano C12H14N2O2 CO2H NH2H N H3C lemborexantum lemborexant (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}- 2-(3-fluorophenyl)-N-(5-fluoropyridin- 2-yl)cyclopropanecarboxamide lemborexant (1R,2S)-2-{[(2,4-diméthylpyrimidin-5-yl)oxy]méthyl}- 2-(3-fluorophényl)-N-(5-fluoropyridin- 2-yl)cyclopropanecarboxamide lemborexant (1R,2S)-2-{[(2,4-dimetilpirimidin-5-il)oxi]metil}- 2-(3-fluorofenil)-N-(5-fluoropiridin- 2-il)ciclopropanocarboxamida C22H20F2N4O2 H N H O N N CH3 F O N FH3C Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 92 lenzilumabum # lenzilumab immunoglobulin G1-kappa, anti-[Homo sapiens CSF2 (colony stimulating factor 2 (granulocyte-macrophage), granulocyte-macrophage colony stimulating factor, GM- CSF)], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-449) [Homo sapiens VH (IGHV1- 3*01 (94.90%) -(IGHD)-IGHJ4*01) [8.8.12] (1-119) - IGHG1*03 (CH1 (120-217), hinge (218-232), CH2 (233- 342), CH3 (343-447), CHS (448-449)) (120-449)], (222- 214')-disulfide with kappa light chain (1'-214') [Homo sapiens V-KAPPA (IGKV3-20*01 (85.40%) -IGKJ4*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dimer (228- 228'':231-231'')-bisdisulfide lenzilumab immunoglobuline G1-kappa, anti-[Homo sapiens CSF2 (facteur 2 stimulant de colonies (granulocyte-macrophage), facteur stimulant des colonies de granulocytes et macrophages, GM-CSF)], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-449) [Homo sapiens VH (IGHV1-3*01 (94.90%) -(IGHD)-IGHJ4*01) [8.8.12] (1-119) -IGHG1*03 (CH1 (120-217), charnière (218-232), CH2 (233-342), CH3 (343-447), CHS (448-449)) (120-449)], (222-214')-disulfure avec la chaîne légère kappa (1'-214') [Homo sapiens V-KAPPA (IGKV3-20*01 (85.40%) - IGKJ4*01) [6.3.9] (1'-107') -IGKC*01 (108'-214')]; dimère (228-228'':231-231'')-bisdisulfure lenzilumab inmunoglobulina G1-kappa, anti-[Homo sapiens CSF2 (factor 2 estimulante de colonias (granulocitos- macrófagos), factor estimulante de colonias de granulocitos y macrófagos, GM-CSF)], anticuerpo monoclonal de Homo sapiens; cadena pesada gamma1 (1-449) [Homo sapiens VH (IGHV1-3*01 (94.90%) -(IGHD)-IGHJ4*01) [8.8.12] (1-119) -IGHG1*03 (CH1 (120-217), bisagra (218-232), CH2 (233- 342), CH3 (343-447), CHS (448-449)) (120-449)], (222- 214')-disulfuro con la ligera kappa (1'-214') [Homo sapiens V-KAPPA (IGKV3-20*01 (85.40%) -IGKJ4*01) [6.3.9] (1'- 107') -IGKC*01 (108'-214')]; dímero (228-228'':231-231'')- bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKASGYSFT NYYIHWVRQA PGQRLEWMGW 50 INAGNGNTKY SQKFQGRVTI TRDTSASTAY MELSSLRSED TAVYYCVRRQ 100 RFPYYFDYWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD 150 YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY 200 ICNVNHKPSN TKVDKRVEPK SCDKTHTCPP CPAPELLGGP SVFLFPPKPK 250 DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS 300 TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL PAPIEKTISK AKGQPREPQV 350 YTLPPSREEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 400 DSDGSFFLYS KLTVDKSRWQ QGNVFSCSVM HEALHNHYTQ KSLSLSPGK 449 Light chain / Chaîne légère / Cadena ligera EIVLTQSPAT LSVSPGERAT LSCRASQSVG TNVAWYQQKP GQAPRVLIYS 50 TSSRATGITD RFSGSGSGTD FTLTISRLEP EDFAVYYCQQ FNKSPLTFGG 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 146-202 263-323 369-427 22''-96'' 146''-202'' 263''-323'' 369''-427'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 222-214' 222''-214''' Inter-H-H (h 11, h 14) 228-228'' 231-231'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 299, 299'' WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 93 lonoctocogum alfa # lonoctocog alfa recombinant DNA derived B domain deleted single-chain human blood coagulation factor VIII, produced in Chinese hamster ovary (CHO) D944 cells, glycoform alfa: des-(765-1652)-human blood coagulation factor VIII (antihemophilic factor, procoagulant component) lonoctocog alfa facteur VIII de coagulation humain dont le domaine B a été supprimé, chaîne unique, produit par les cellules ovariennes de hamsters chinois (CHO) D944 à partir d'ADN recombinant, forme glycosylée alfa; dès-(765-1652)-facteur VIII de coagulation humain (facteur antihémophilique, composé procoagulant) lonoctocog alfa factor VIII de coagulación humano al que se ha suprimido el dominio B, monocatenario, producido por células ováricas de hamster chino (CHO) D944 a partir de ADN recombinante, forma glicosilada alfa; des-(765-1652)-factor VIII de coagulación humano (factor antihemofílico, componente procoagulante) CO2H NH2H O S HO O O Glycosylation sites (N) / Sites de glycosylation (N) / Posiciones de glicosilación (N) Asn-41 Asn-239 Asn-757 Asn-764 Asn-922 Asn-1230 Glycosylation site (O) / Site de glycosylation (O) / Posición de glicosilación (O) Ser-743 Sequence / Séquence / Secuencia ATRRYYLGAV ELSWDYMQSD LGELPVDARF PPRVPKSFPF NTSVVYKKTL 50 FVEFTDHLFN IAKPRPPWMG LLGPTIQAEV YDTVVITLKN MASHPVSLHA 100 VGVSYWKASE GAEYDDQTSQ REKEDDKVFP GGSHTYVWQV LKENGPMASD 150 PLCLTYSYLS HVDLVKDLNS GLIGALLVCR EGSLAKEKTQ TLHKFILLFA 200 VFDEGKSWHS ETKNSLMQDR DAASARAWPK MHTVNGYVNR SLPGLIGCHR 250 KSVYWHVIGM GTTPEVHSIF LEGHTFLVRN HRQASLEISP ITFLTAQTLL 300 MDLGQFLLFC HISSHQHDGM EAYVKVDSCP EEPQLRMKNN EEAEDYDDDL 350 TDSEMDVVRF DDDNSPSFIQ IRSVAKKHPK TWVHYIAAEE EDWDYAPLVL 400 APDDRSYKSQ YLNNGPQRIG RKYKKVRFMA YTDETFKTRE AIQHESGILG 450 PLLYGEVGDT LLIIFKNQAS RPYNIYPHGI TDVRPLYSRR LPKGVKHLKD 500 FPILPGEIFK YKWTVTVEDG PTKSDPRCLT RYYSSFVNME RDLASGLIGP 550 LLICYKESVD QRGNQIMSDK RNVILFSVFD ENRSWYLTEN IQRFLPNPAG 600 VQLEDPEFQA SNIMHSINGY VFDSLQLSVC LHEVAYWYIL SIGAQTDFLS 650 VFFSGYTFKH KMVYEDTLTL FPFSGETVFM SMENPGLWIL GCHNSDFRNR 700 GMTALLKVSS CDKNTGDYYE DSYEDISAYL LSKNNAIEPR SFSQNSRHPS 750 TRQKQFNATT IPENTTLQSD QEEIDYDDTI SVEMKKEDFD IYDEDENQSP 800 RSFQKKTRHY FIAAVERLWD YGMSSSPHVL RNRAQSGSVP QFKKVVFQEF 850 TDGSFTQPLY RGELNEHLGL LGPYIRAEVE DNIMVTFRNQ ASRPYSFYSS 900 LISYEEDQRQ GAEPRKNFVK PNETKTYFWK VQHHMAPTKD EFDCKAWAYF 950 SDVDLEKDVH SGLIGPLLVC HTNTLNPAHG RQVTVQEFAL FFTIFDETKS 1000 WYFTENMERN CRAPCNIQME DPTFKENYRF HAINGYIMDT LPGLVMAQDQ 1050 RIRWYLLSMG SNENIHSIHF SGHVFTVRKK EEYKMALYNL YPGVFETVEM 1100 LPSKAGIWRV ECLIGEHLHA GMSTLFLVYS NKCQTPLGMA SGHIRDFQIT 1150 ASGQYGQWAP KLARLHYSGS INAWSTKEPF SWIKVDLLAP MIIHGIKTQG 1200 ARQKFSSLYI SQFIIMYSLD GKKWQTYRGN STGTLMVFFG NVDSSGIKHN 1250 IFNPPIIARY IRLHPTHYSI RSTLRMELMG CDLNSCSMPL GMESKAISDA 1300 QITASSYFTN MFATWSPSKA RLHLQGRSNA WRPQVNNPKE WLQVDFQKTM 1350 KVTGVTTQGV KSLLTSMYVK EFLISSSQDG HQWTLFFQNG KVKVFQGNQD 1400 SFTPVVNSLD PPLLTRYLRI HPQSWVHQIA LRMEVLGCEA QDLY 1444 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 153-179 248-329 528-554 630-711 944-970 1011-1015 1133-1281 1286-1438 Modified residues / Résidus modifiés / Restos modificados Y 346-718-719-723-776-792 O-sulfoTyr lulizumabum pegolum # lulizumab pegol immunoglobulin V-kappa pegylated, anti-[Homo sapiens CD28 (TP44, T cell specific surface glycoprotein CD28)], humanized monoclonal antibody; V-kappa domain (1-107) [humanized V-KAPPA (Homo sapiens IGKV1D-13*01 (84.30%) D86>C (70) -IGKJ1*01 G119>S (99)) [6.3.9] (1-107)] -arginyl (108); conjugated via a linker of the maleimide group (thioether bond with cysteinyl 86 (70)) to two linear chains of methoxy polyethylene glycol 20 (mPEG20) Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 94 lulizumab pégol immunoglobuline V-kappa pégylé, anti-[Homo sapiens CD28 (TP44, glycoprotéine de surface CD28 spécifique des cellules T)], anticorps monoclonal humanisé; domaine V-kappa (1-107) [V-KAPPA humanisé (Homo sapiens IGKV1D-13*01 (84.30%) D86>C (70) -IGKJ1*01 G119>S (99)) [6.3.9] (1-107)] -arginyl (108); conjugué via un linker du groupe maléimide (liaison thioéther avec cystéinyl 86 (70)) à deux chaînes linéaires de méthoxy polyéthylène glycol 20 (mPEG20) lulizumab pegol inmunoglobulina V-kappa pegilada, anti-[Homo sapiens CD28 (TP44, glicoproteína de superficie CD28 específico de células T)], anticuerpo monoclonal humanizado; dominio V-kappa (1-107) [V-KAPPA humanizado (Homo sapiens IGKV1D-13*01 (84.30%) D86>C (70) -IGKJ1*01 G119>S (99)) [6.3.9] (1-107)] -arginil (108); conjugado mediante conector del grupo maleimida (unión tioéter con cisteinil 86 (70)) con dos cadenas lineales de metoxi polietilen glicol 20 (mPEG20) DIQMTQSPSS LSASVGDRVT ITCRASRPIW PFLEWYQQKP GKAPKLLIYF 50TSRLRHGVPS RFSGSGSGTC FTLTISSLQP EDFATYYCLQ NVANPATFSQ 100 GTKVEIKR 108 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-L (C23-C104) 23-88 Pegylation site / Site de pegylation / Posición de pegilación D86>C: 70 lumretuzumabum # lumretuzumab immunoglobulin G1-kappa, anti-[Homo sapiens ERBB3 (receptor tyrosine-protein kinase erbB-3, HER3)], humanized monoclonal antibody; gamma1 heavy chain (1-449) [humanized VH (Homo sapiens IGHV1-18*01 (89.80%) -(IGHD)-IGHJ4*01) [8.8.13] (1-120) -Homo sapiens IGHG1*01(CH1 (121-218), hinge (219-233), CH2 (234-343), CH3 (344-448), CHS K2>del (449)) (121-449)],(223-220')-disulfide with kappa light chain (1’-220’) [humanized V-KAPPA (Homo sapiens IGKV4-1*01 (93.10%) -IGKJ2*01) [12.3.9] (1'-113') -Homo sapiens IGKC*01 (114'-220')]; dimer (229-229":232-232")- bisdisulfide lumrétuzumab immunoglobuline G1-kappa, anti-[Homo sapiens ERBB3 (récepteur tyrosine-protéine kinase erbB3, HER3)], anticorps monoclonal humanisé; chaîne lourde gamma1 (1-449) [VH humanisé (Homo sapiensIGHV1-18*01 (89.80%) -(IGHD)-IGHJ4*01) [8.8.13] (1-120) -Homo sapiens IGHG1*01(CH1 (121-218), charnière (219-233), CH2 (234-343), CH3 (344-448), CHS K2>del (449)) (121-449)],(223-220')-disulfure avec la chaîne légère kappa (1’-220’) [V-KAPPA humanisé (Homo sapiens IGKV4-1*01 (93.10%) -IGKJ2*01) [12.3.9] (1'-113') -Homo sapiens IGKC*01 (114'-220')]; dimère (229- 229":232-232")-bisdisulfure WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 95 lumretuzumab inmunoglobulina G1-kappa, anti-[Homo sapiens ERBB3 (receptor tirosina-proteína kinasa erbB3, HER3)], anticuerpo monoclonal humanizado; cadena pesada gamma1 (1-449) [VH humanizada (Homo sapiens IGHV1-18*01 (89.80%) -(IGHD)-IGHJ4*01) [8.8.13] (1-120) -Homo sapiens IGHG1*01 (CH1 (121- 218), bisagra (219-233), CH2 (234-343), CH3 (344-448), CHS K2>del (449)) (121-449)], (223-220')-disulfuro con la cadena ligera kappa (1’-220’) [V-KAPPA humanizada (Homo sapiens IGKV4-1*01 (93.10%) -IGKJ2*01) [12.3.9] (1'-113') -Homo sapiens IGKC*01 (114'-220')]; dímero (229-229":232-232")-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKASGYTFR SSYISWVRQA PGQGLEWMGW 50 IYAGTGSPSY NQKLQGRVTM TTDTSTSTAY MELRSLRSDD TAVYYCARHR 100 DYYSNSLTYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK 150 DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT 200 YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP 250 KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 300 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ 350 VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV 400 LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPG 449 Light chain / Chaîne légère / Cadena ligera DIVMTQSPDS LAVSLGERAT INCKSSQSVL NSGNQKNYLT WYQQKPGQPP 50 KLLIYWASTR ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQSDYSY 100 PYTFGQGTKL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA 150 KVQWKVDNAL QSGNSQESVT EQDSKDSTYS LSSTLTLSKA DYEKHKVYAC 200 EVTHQGLSSP VTKSFNRGEC 220 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 147-203 264-324 370-428 22''-96'' 147''-203'' 264''-324'' 370''-428'' Intra-L (C23-C104) 23'-94' 140'-200' 23'''-94''' 140'''-200''' Inter-H-L (h 5-CL 126) 223-220' 223''-220''' Inter-H-H (h 11, h 14) 229-229'' 232-232'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 300, 300'' Enriched in bisected non-fucosylated oligosaccharides Enrichi en oligosaccharides non-fucosylés bissectés Enriquecido con oligosacáridos bisecados no fucosilados Other post-translational modifications Autres modifications post-traductionnelles Otras modificaciones post-traduccionales Lacking H chain C-terminal lysine (CHS K2>del) merotocinum merotocin N-(4-sulfanylbutanoyl)-L-tyrosyl-L-isoleucyl-L-glutaminyl- L-asparaginyl-L-cysteinyl-N-[(4-fluorophenyl)methyl]glycyl- L-leucylglycinamide cyclic (1-5)-thioether mérotocine (1-5)-thioéthercyclique du N-(4-sulfanylbutanoyl)-L-tyrosyl- L-isoleucyl-L-glutaminyl-L-asparaginyl-L-cystéinyl- N-[(4-fluorophényl)méthyl]glycyl-L-leucylglycinamide merotocina (1-5)-tioetercíclico del N-(4-sulfanilbutanoil)-L-tirosil- L-isoleucil-L-glutaminil-L-asparaginil-L-cisteinil- N-[(4-fluorofenil)metil]glicil-L-leucilglicinamida C48H68FN11O12S Tyr Ile Gln Asn N H Leu Gly NH2 O H O S N O F Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 96 mibenratidum mibenratide an 18 amino acid cyclic peptide largely homologous to amino acids 202-220 of the β1-adrenergic receptor second extracellular loop (AR-ECII) that binds to anti-β1-AR pathological autoantibodies: cyclo(L-alanyl-L-arginyl-L-arginyl-L-cysteinyl-L-tyrosyl- L-asparaginyl-L-α-aspartyl-L-prolyl-L-lysyl-L-cysteinyl- L-seryl-L-α-aspartyl-L-phenylalanyl-L-valyl-L-glutaminyl- L-alanyl-L-α-aspartyl-L-α-glutamyl), cyclic (4-10)-disulfide mibenratide peptide cyclique de 18 acides aminés largement homologue aux acides aminés 202-220 de la seconde boucle extracellulaire de l'adrénorécepteur β1 (AR-ECII) qui se lie aux autoanticorps anti-β1-AR pathologiques: (4-10)-disulfure cyclique du cyclo(L-alanyl-L-arginyl- L-arginyl-L-cystéinyl-L-tyrosyl-L-asparaginyl-L-α-aspartyl- L-prolyl-L-lysyl-L-cystéinyl-L-séryl-L-α-aspartyl- L-phénylalanyl-L-valyl-L-glutaminyl-L-alanyl-L-α-aspartyl- L-α-glutamyl) mibenratida péptido cíclico de 18 aminoácidos altamente homólogo a los aminoácidos 202-220 del segundo bucle extracelular del adrenoreceptor β1 (AR-ECII) que se une a los autoanticuerpos anti-β1-AR patológicos: (4-10)-disulfuro cíclico del ciclo (L-alanil-L-arginil-L-arginil- L-cisteinil-L-tirosil-L-asparaginil-L-α-aspartil-L-prolil-L-lisil- L-cisteinil-L-seril-L-α-aspartil-L-fenilalanil-L-valil-L-glutaminil- L-alanil-L-α-aspartil-L-α-glutamil) C87H129N27O30S2 1 1018 Glu Ala Asp Arg Ala Arg Gln Cys Val Tyr Phe Asn Asp Asp Ser Pro Cys Lys modimelanotidum modimelanotide acetylhexa-L-lysyl[human melanotropin alpha (alpha-MSH)] modimélanotide acétylhexa-L-lysyl[mélanotropine alpha humaine (alpha- MSH)] modimelanotida acetilhexa-L-lisil[melanotropina alfa humana (alfa-MSH)] C113H181N33O25S Lys Lys Lys Lys Lys Lys Ser Tyr Ser Met O H3C Glu His Phe Arg Trp Gly Lys Pro Val NH2 10 19 WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 97 mongersenum mongersen all-P-ambo-2'-deoxy-P-thioguanylyl-(3'→5')-P- thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl- (3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-P- thiocytidylyl-(3'→5')-2'-deoxy-P-thiocytidylyl-(3'→5')-2'- deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thiocytidylyl- (3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')- 2'-deoxy-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'- deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thiocytidylyl- (3'→5')-2'-deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy-5-methyl- P-thiocytidylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'- deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thioadenylyl- (3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxycytidine mongersen tout-P-ambo-2'-déoxy-P-thioguanylyl-(3'→5')-P- thiothymidylyl-(3'→5')-2'-déoxy-5-méthyl-P-thiocytidylyl- (3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-2'-déoxy-P- thiocytidylyl-(3'→5')-2'-déoxy-P-thiocytidylyl-(3'→5')-2'- déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy-P-thiocytidylyl- (3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')- 2'-déoxy-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'- déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy-P-thiocytidylyl- (3'→5')-2'-déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy-5-méthyl- P-thiocytidylyl-(3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-2'- déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy-P-thioadénylyl- (3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-2'-déoxycytidine mongersén todo-P-ambo-2'-desoxi-P-tioguanilil-(3'→5')-P-tiotimidilil- (3'→5')-2'-desoxi-5-metil-P-tiocitidilil-(3'→5')-2'-desoxi-P- tioguanilil-(3'→5')-2'-desoxi-P-tioctidlil-(3'→5')-2'-desoxi-P- tiocitidilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-2'-desoxi-P- tiocitidilil-(3'→5')-P-tiotimidilil-(3'→5')-P-tiotimidilil-(3'→5')- 2'-desoxi-P-tiocitidilil-(3'→5')-P-tiotimidilil-(3'→5')-2'-desoxi- P-tiocitidilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-2'-desoxi- P-tiocitidilil-(3'→5')-2'-desoxi-5-metil-P-tiocitidilil-(3'→5')-2'- desoxi-P-tioguanilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-2'- desoxi-P-tioadenilil-(3'→5')-2'-desoxi-P-tioguanilil-(3'→5')- 2'-desoxicitidina C200H261N69O107P20S20 (3'-5')d(P-thio)(G-T-m5C-G-C-C-C-C-T-T-C-T-C-C-C-m5C-G-C-A-G-C) N NO NH2 O HO CH3 m5C HO napabucasinum napabucasin 2-acetylnaphtho[2,3-b]furan-4,9-dione napabucasine 2-acétylnaphtho[2,3-b]furan-4,9-dione napabucasina 2-acetilnafto[2,3-b]furan-4,9-diona Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 98 C14H8O4 O O O CH3 O odalasvirum odalasvir dimethyl N,N'-(1,4(1,4)-dibenzenacyclohexaphane- 12,42-diylbis{1H-benzimidazole-5,2-diyl[(2S,3aS,7aS)- octahydro-1H-indole-2,1-diyl][(2S)-3-methyl-1-oxobutan- 1,2-diyl]})biscarbamate odalasvir N,N'-(1,4(1,4)-dibenzénacyclohexaphane-12,42-diylbis{1H- benzimidazole-5,2-diyl[(2S,3aS,7aS)-octahydro-1H-indole- 2,1-diyl][(2S)-3-méthyl-1-oxobutan-1,2-diyl]})biscarbamate de diméthyle odalasvir N,N'-(1,4(1,4)-dibencenaciclohexafano-12,42-diilbis{1H- benzoimidazol-5,2-diil[(2S,3aS,7aS)-octahidro-1H-indol- 2,1-diil][(2S)-3-metil-1-oxobutan-1,2-diil]})biscarbamato de dimetilo C60 H72 N8 O6 N H N N H O N H H CH3 H3C O OH3C H H N N H N H O H N H H3C CH3 O O CH3 H H olipudasum alfa # olipudase alfa recombinant DNA derived des-(1-13)-human sphingomyelin phosphodiesterase (acid sphingomyelinase, EC-3.1.4.12), produced in Chinese hamster ovary (CHO) cells, glycoform alfa olipudase alfa dès-(1-13)-sphingomyéline phosphodiesterase humaine (sphingomyélinase acide, EC-3.1.4.12), produite par des cellules ovariennes de hamster chinois à partir d'ADN recombinant, forme glycosylée alfa olipudasa alfa des-(1-13)-esfingomielina fosfodiesterasa humana (esfingomielinasa ácida, EC-3.1.4.12), producida en células ováricas de hamster chino a partir de ADN recombinante, forma glicosilada alfa WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 99 Glycosylation sites (N) / Sites de glycosylation (N) / Posiciones de glicosilación (N) Asn-40 Asn-129 Asn-289 Asn-349 Asn-457 Asn-474 Sequence / Séquence / Secuencia HPLSPQG HPARLHRIVP RLRDVFGWGN LTCPICKGLF 50 TAINLGLKKE PNVARVGSVA IKLCNLLKIA PPAVCQSIVH LFEDDMVEVW 100 RRSVLSPSEA CGLLLGSTCG HWDIFSSWNI SLPTVPKPPP KPPSPPAPGA 150 PVSRILFLTD LHWDHDYLEG TDPDCADPLC CRRGSGLPPA SRPGAGYWGE 200 YSKCDLPLRT LESLLSGLGP AGPFDMVYWT GDIPAHDVWH QTRQDQLRAL 250 TTVTALVRKF LGPVPVYPAV GNHESTPVNS FPPPFIEGNH SSRWLYEAMA 300 KAWEPWLPAE ALRTLRIGGF YALSPYPGLR LISLNMNFCS RENFWLLINS 350 TDPAGQLQWL VGELQAAEDR GDKVHIIGHI PPGHCLKSWS WNYYRIVARY 400 ENTLAAQFFG HTHVDEFEVF YDEETLSRPL AVAFLAPSAT TYIGLNPGYR 450 VYQIDGNYSG SSHVVLDHET YILNLTQANI PGAIPHWQLL YRARETYGLP 500 NTLPTAWHNL VYRMRGDMQL FQTFWFLYHK GHPPSEPCGT PCRLATLCAQ 550 LSARADSPAL CRHLMPDGSL PEAQSLWPRP LFC 583 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 43-119 46-111 74-85 175-180 181-204 339-385 538-542 548-561 omipalisibum omipalisib 2,4-difluoro-N-{2-methoxy-5-[4-(pyridazin-4-yl)quinolin- 6-yl]pyridin-3-yl}benzenesulfonamide omipalisib 2,4-difluoro-N-{2-méthoxy-5-[4-(pyridazin-4-yl)quinoléin- 6-yl]pyridin-3-yl}benzènesulfonamide omipalisib 2,4-difluoro-N-{2-metoxi-5-[4-(piridazin-4-il)quinolein- 6-il]piridin-3-il}bencenosulfonamida C25H17F2N5O3S NH3CO H N S F F O O N N N orilotimodum orilotimod D-γ-glutamyl-D-tryptophan orilotimod D-γ-glutamyl-D-tryptophane orilotimod D-γ-glutamil-D-triptófano C16H19N3O5 H N CO2H H HO2C N H O NH2H paritaprevirum paritaprevir (2R,6S,12Z,13aS,14aR,16aS)-N-(cyclopropylsulfonyl)- 6-(5-methylpyrazin-2-carboxamido)-5,16-dioxo- 2-(phenanthridin-6-yloxy)- 1,2,3,6,7,8,9,10,11,13a,14,15,16,16a- tetradecahydrocyclopropa[e]pyrrolo[1,2- a][1,4]diazacyclopentadecine-14a(5H)-carboxamide Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 100 paritaprévir (2R,6S,12Z,13aS,14aR,16aS)-N-(cyclopropylsulfonyl)- 6-(5-méthylpyrazin-2-carboxamido)-5,16-dioxo- 2-(phénanthridin-6-yloxy)- 1,2,3,6,7,8,9,10,11,13a,14,15,16,16a- tétradécahydrocyclopropa[e]pyrrolo[1,2- a][1,4]diazacyclopentadécine-14a(5H)-carboxamide paritaprevir (2R,6S,12Z,13aS,14aR,16aS)-N-(ciclopropilsulfonil)- 6-(5-metilpirazin-2-carboxamido)-5,16-dioxo-2-(fenantridin-6- iloxi)-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a- tetradecahidrociclopropa[e]pirrolo[1,2- a][1,4]diazaciclopentadecina-14a(5H)-carboxamida C40H43N7O7S N N H O O H H H HN H O O O NH S O O N N N CH3 pasotuxizumabum # pasotuxizumab immunoglobulin scFv-scFv, anti-[Homo sapiens FOLH1 (folate hydrolase, prostate specific membrane antigen, PSMA)]/anti- [Homo sapiens CD3E (CD3 epsilon)], humanized and chimeric monoclonal antibody bispecific single chain; scFv anti-FOLH1 (1-243) [humanized VH (Homo sapiens IGHV3-11*01 (85.70%)-(IGHD)-IGHJ4*01) [8.8.14](1-121)-15- mer tris(tetraglycyl-seryl) linker (122-136) -humanized V-KAPPA (Homo sapiens IGKV1-16*01 (81.10%)- IGKJ2*01Q120>G (236)) [6.3.9](137-243)] -6-mer seryl- tetraglycyl-seryl linker (244-249) -scFv anti-CD3E (250-498) [Mus musculus VH (Mus musculus IGHV10-1*02 (91.90%)- (IGHD)-IGHJ3*01) [8.10.16] (250-374) -15-mer tris(tetraglycyl- seryl) linker (375-389) -humanized V-LAMBDA (Homo sapiens IGLV7-43*01(85.10%)-IGLJ3*02 [9.3.9] (390-498)] -hexahistidine (499-504) pasotuxizumab immunoglobuline scFv-scFv, anti-[Homo sapiens FOLH1 (folate hydrolase, antigène membranaire spécifique de la prostate, PSMA)]/anti-[Homo sapiens CD3E (CD3 epsilon)], anticorps monoclonal humanisé et chimérique bispécifique à chaîne unique; scFv anti-FOLH1(1-243) [VH humanisé (Homo sapiens IGHV3- 11*01 (85.70%)-(IGHD)-IGHJ4*01) [8.8.14](1-121)-15-mer tris(tétraglycyl-séryl) linker (122-136) - V-KAPPA humanisé (Homo sapiens IGKV1-16*01 (81.10%)-IGKJ2*01Q120>G (236)) [6.3.9](137-243)] -6-mer séryl-tétraglycyl-séryl linker (244-249) -scFv anti-CD3E (250-498) [Mus musculus VH (Mus musculus IGHV10-1*02 (91.90%)-(IGHD)-IGHJ3*01) [8.10.16] (250-374) -15-mer tris(tétraglycyl-séryl) linker (375-389) – V-LAMBDA humanisé (Homo sapiens IGLV7-43*01(85.00%)- IGLJ3*02 [9.3.9] (390-498)] -hexahistidine (499-504) WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 101 pasotuxizumab inmunoglobulina scFv-scFv, anti-[Homo sapiens FOLH1 (folato hidrolasa, antígeno de membrana específico de la próstata, PSMA)]/anti-[Homo sapiens CD3E (CD3 épsilon)], anticuerpo monoclonal humanizado y quimérico biespecífico monocatenario; IGHV3-11*01 (85.70%)-(IGHD)-IGHJ4*01) [8.8.14] (1-121) -15-mer tris(tetraglicil-seril) conector (122-136) - V-KAPPA humanizado (Homo sapiens IGKV1-16*01 (81.10%)- IGKJ2*01Q120>G (236)) [6.3.9] (137-243)] -6-mer seril- tetraglicil-seril conector (244-249) -scFv anti-CD3E (250- 498) [Mus musculus VH (Mus musculus IGHV10-1*02 (91.90%)-(IGHD)-IGHJ3*01) [8.10.16] (250-374) -15-mer tris(tetraglicil-seril) conector 375-389) -V-LAMBDA humanizado (Homo sapiens IGLV7-43*01(85.00%)- IGLJ3*02 [9.3.9] (390-498)] -hexahistidina (499-504) QVQLVESGGG LVKPGESLRL SCAASGFTFS DYYMYWVRQA PGKGLEWVAI 50ISDGGYYTYY SDIIKGRFTI SRDNAKNSLY LQMNSLKAED TAVYYCARGF 100 PLLRHGAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSDIQM TQSPSSLSAS 150 VGDRVTITCK ASQNVDTNVA WYQQKPGQAP KSLIYSASYR YSDVPSRFSG 200 SASGTDFTLT ISSVQSEDFA TYYCQQYDSY PYTFGGGTKL EIKSGGGGSE 250 VQLVESGGGL VQPGGSLKLS CAASGFTFNK YAMNWVRQAP GKGLEWVARI 300 RSKYNNYATY YADSVKDRFT ISRDDSKNTA YLQMNNLKTE DTAVYYCVRH 350 GNFGNSYISY WAYWGQGTLV TVSSGGGGSG GGGSGGGGSQ TVVTQEPSLT 400 VSPGGTVTLT CGSSTGAVTS GNYPNWVQQK PGQAPRGLIG GTKFLAPGTP 450 ARFSGSLLGG KAALTLSGVQ PEDEAEYYCV LWYSNRWVFG GGTKLTVLHH 500 HHHH 504 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-chain C23 C104 22-96 159-224 271-347 411-479 patidegibum patidegib N-[(2S,3R,3'R,3aS,4'aR,6S,6'aR,6'bS,7aR,12'aS,12'bS)- 3,6,11',12'b-tetramethyl- 2',3',3a,4,4',4'a,5,5',6,6',6'a,6'b,7,7',7a,8',10',12',12'a,12'b- icosahydro-1'H,3H-spiro[furo[3,2-b]pyridine-2,9'- naphtho[2,1-a]azulen]-3'-yl]methanesulfonamide patidégib N-[(2S,3R,3'R,3aS,4'aR,6S,6'aR,6'bS,7aR,12'aS,12'bS)- 3,6,11',12'b-tétraméthyl- 2',3',3a,4,4',4'a,5,5',6,6',6'a,6'b,7,7',7a,8',10',12',12'a,12'b- icosahydro-1'H,3H-spiro[furo[3,2-b]pyridine-2,9'- naphto[2,1-a]azulen]-3'-yl]méthanesulfonamide patidegib N-[(2S,3R,3'R,3aS,4'aR,6S,6'aR,6'bS,7aR,12'aS,12'bS)- 3,6,11',12'b-tetrametil- 2',3',3a,4,4',4'a,5,5',6,6',6'a,6'b,7,7',7a,8',10',12',12'a,12'b- icosahidro-1'H,3H-espiro[furo[3,2-b]piridina-2,9'-nafto[2,1- a]azulen]-3'-il]metanosulfonamida C29H48N2O3S N H S H3C OO CH3 H H H H H3C H O HNH H3C H H CH3 H Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 102 peficitinibum peficitinib 4-{[(1R,2s,3S,5s,7s)-5-hydroxyadamantan-2-yl]amino}- 1H-pyrrolo[2,3-b]pyridine-5-carboxamide péficitinib 4-{[(1R,2s,3S,5s,7s)-5-hydroxyadamantan-2-yl]amino}- 1H-pyrrolo[2,3-b]pyridine-5-carboxamide peficitinib 4-{[(1R,2s,3S,5s,7s)-5-hidroxiadamantan-2-il]amino}- 1H-pirrolo[2,3-b]piridina-5-carboxamida C18H22N4O2 N H2N O H N HO NH pegargiminasum # pegargiminase [111-glutamic acid,209-serine]arginine deiminase (ADI, arginine dihydrolase, AD) from Mycoplasma hominis, an average of five amino groups are amidified with 4-[ω-methoxypoly(oxyethylene)]-4-oxobutanoyl, produced in Escherichia coli pégargiminase [111-acide glutamique,209-sérine]arginine désiminase (ADI, arginine dihydrolase, AD) de Mycoplasma hominis, produite par Escherichia coli, et dont cinq groupes amino, en moyenne, sont amidifiés par le 4-[ω-méthoxypoly(oxyéthylène)]-4-oxobutanoyle pegargiminasa [111-ácido glutámico,209-seria]arginina desiminasa (ADI, arginina dihidrolasa, AD) de Mycoplasma hominis, producida en Escherichia coli, en la cual 5 grupos amino por término medio, están amidificado por 4-[ω-metoxipoli(oxietileno)]-4-oxobutanoilo C2091H3276N540O607S15 ((C5H6O3(C2H4O)n)a C O O O H3CO n R- = H- or/ou/o N H CO2H H R HO H2N CO2H H NHR S 1 K 6-55-62-65-87-90-110-120-135-194 197-207-241-244-247-252-261-277-279 291-315-323-355-367-373-404-407 * an average of 5 (a) out of 28 are pegylated / 5 (a) sur les 28 sont en moyenne pégylés / 5 (a) cada 28 por térnino medio están pegilados Sequence / Séquence / Secuencia SVFDSKFNGI HVYSEIGELE TVLVHEPGRE IDYITPARLD ELLFSAILES 50 HDARKEHQSF VKIMKDRGIN VVELTDLVAE TYDLASKAAK EEFIETFLEE 100 TVPVLTEANK EAVRAFLLSK PTHEMVEFMM SGITKYELGV ESENELIVDP 150 MPNLYFTRDP FASVGNGVTI HFMRYIVRRR ETLFARFVFR NHPKLVKTPW 200 YYDPAMKMSI EGGDVFIYNN ETLVVGVSER TDLDTITLLA KNIKANKEVE 250 FKRIVAINVP KWTNLMHLDT WLTMLDKNKF LYSPIANDVF KFWDYDLVNG 300 GAEPQPQLNG LPLDKLLASI INKEPVLIPI GGAGATEMEI ARETNFDGTN 350 YLAIKPGLVI GYDRNEKTNA ALKAAGITVL PFHGNQLSLG MGNARCMSMP 400 LSRKDVKW 408 Potential modified residues* / Résidus modifiables* / Restos potencialemente modificados* WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 103 pegcrisantaspasum # pegcrisantaspase recombinant L-asparaginase derived from Erwinia chrysanthemi pegylated with 5 kDa methoxy polyethylene glycol (m-PEG-NHS), produced in Escherichia coli: L-asparaginase (EC 3.5.1.1, L-asparagine amidohydrolase) Erwinia chrysanthemi tetramer α4, an average of 10 (a) out of 18 amino groups of each monomer are amidified with 5-{[α-methylpoly(oxyethylene)]amino}-5-oxopentanoyl pegcrisantaspase L-asparaginase recombinante dérivée d’Erwinia chrysanthemi pégylée par du méthoxy polyéthylène glycol (m-PEG-NHS) de 5kDa, produite par Escherichia coli: tétramère α4 de la L-asparaginase (EC 3.5.1.1, L-asparagine amidohydrolase) d’Erwinia chrysanthemi dont 10 (a) groupes amino, en moyenne, sur les 18 de chaque monomère sont amidifiés par le radical substituant 5-{[α- méthylpoly(oxyéthylène)]amino}-5-oxopentanoyle pegcrisantaspasa L-asparaginasa recombinante derivada de Erwinia chrysanthemi pegilada por metoxi polietilenglicol (m-PEG- NHS) de 5kDa, producida en Escherichia coli: tetrámero α4 de la L-asparaginasa (EC 3.5.1.1, L-asparagina amidohidrolasa) d’Erwinia chrysanthemi de la cual 10 (a) grupos amino, por término medio, de los 18 de cada monómero están amidificados por 5-{[α- metilpoli(oxietileno)]amino}-5-oxopentanoilo C1546H2510N432O476S9(C6H9NO2[C2H4O]n)a (monomer) O H3C O H N O C n K 3-30-47-48-53-72-110-113-145-168 178-201-219-243-265-269-318 H2N CO2H HNHR n # 120 R = H or / ou / ó N H CO2H HH3C RA1 Monomer sequence / Séquence du monomère/ Secuencia del monómero ADKLPNIVIL ATGGTIAGSA ATGTQTTGYK AGALGVDTLI NAVPEVKKLA 50 NVKGEQFSNM ASENMTGDVV LKLSQRVNEL LARDDVDGVV ITHGTDTVEE 100 SAYFLHLTVK SDKPVVFVAA MRPATAISAD GPMNLLEAVR VAGDKQSRGR 150 GVMVVLNDRI GSARYITKTN ASTLDTFKAN EEGYLGVIIG NRIYYQNRID 200 KLHTTRSVFD VRGLTSLPKV DILYGYQDDP EYLYDAAIQH GVKGIVYAGM 250 GAGSVSVRGI AGMRKAMEKG VVVIRSTRTG NGIVPPDEEL PGLVSDSLNP 300 AHARILLMLA LTRTSDPKVI QEYFHTY 327 Potential modified residues / Résidus modifiés potentiels / Restos potencialmente modificados pegvaliasum # pegvaliase pegylated, recombinant DNA derived Anabaena variabilis phenylalanine ammonia lyase mutein (S 503, S 565), produced in Escherichia coli: [503,565-diserine (C>S)]phenylalanine ammonia-lyase (EC 4.3.1.24) Anabaena variabilis in which an average of 5 lysyl residues are N6-{6-[ω- methoxypoly(oxyethylene)]hexanoyl} substituted pegvaliase mutéine (S 503, S 565) de phénylalanine ammoniac-lyase de Anabaena variabilis, pégylée, produite par Escherichia coli à partir d'ADN recombinant: [503,565-disérine (C>S)]phénylalanine ammoniac-lyase (EC 4.3.1.24) de Anabaena variabilis dont une moyenne de 5 résidus lysyl sont N6-{6-[ω- méthoxypoly(oxyéthylène)]hexanoyl} substitués Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 104 pegvaliasa muteína (S 503, S 565) de la fenilalanina amoniaco-liasa de Anabaena variabilis, pegilada, producida en Escherichia coli a partir de ADN recombinante: [503,565-diserine (C>S)]fenilalanina amoniaco-liase (EC 4.3.1.24) de Anabaena variabilis de cuyos restos lisil 5, por término medio, están N6-{6-[ω- metoxipoli(oxietileno)]hexanoil} substituidos C2726H4321N763O828S20 (C7H12O2[C2H4O]n)a C O H3CO n H2N CO2H H NHR R- = H- or/ou/o O 4 O H N H CH3 N N CH2 O K 10, 32, 115, 145, 195, 301, 335, 413, 493, 494, 522 Partly pegylated Lysyl Lysyl partiellement pégylé Lisil parcialmente pegilado ASG 167-168-169 Dianhydroderivative Modified residues / Résidus modifiés / Restos modificados Sequence / Séquence / Secuencia MKTLSQAQSK TSSQQFSFTG NSSANVIIGN QKLTINDVAR VARNGTLVSL 50 TNNTDILQGI QASCDYINNA VESGEPIYGV TSGFGGMANV AISREQASEL 100 QTNLVWFLKT GAGNKLPLAD VRAAMLLRAN SHMRGASGIR LELIKRMEIF 150 LNAGVTPYVY EFGSIGASGD LVPLSYITGS LIGLDPSFKV DFNGKEMDAP 200 TALRQLNLSP LTLLPKEGLA MMNGTSVMTG IAANCVYDTQ ILTAIAMGVH 250 ALDIQALNGT NQSFHPFIHN SKPHPGQLWA ADQMISLLAN SQLVRDELDG 300 KHDYRDHELI QDRYSLRCLP QYLGPIVDGI SQIAKQIEIE INSVTDNPLI 350 DVDNQASYHG GNFLGQYVGM GMDHLRYYIG LLAKHLDVQI ALLASPEFSN 400 GLPPSLLGNR ERKVNMGLKG LQICGNSIMP LLTFYGNSIA DRFPTHAEQF 450 NQNINSQGYT SATLARRSVD IFQNYVAIAL MFGVQAVDLR TYKKTGHYDA 500 RASLSPATER LYSAVRHVVG QKPTSDRPYI WNDNEQGLDE HIARISADIA 550 AGGVIVQAVQ DILPSLH 567 polmacoxibum polmacoxib 4-[3-(3-fluorophenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran- 2-yl]-benzenesulfonamide polmacoxib 4-[3-(3-fluorophényl)-5,5-diméthyl-4-oxo-4,5-dihydrofuran- 2-yl]-benzènesulfonamide polmacoxib 4-[3-(3-fluorofenil)-5,5-dimetil-4-oxo-4,5-dihidrofuran-2-il]- bencenosulfonamida C18H16FNO4S S NH2 OO O H3C CH3 F O presatovirum presatovir N-(2-{[(2S)-2-{5-[(3S)-3-aminopyrrolidin-1-yl]- 6-methylpyrazolo[1,5-a]pyrimidin-2-yl}piperidin- 1-yl]carbonyl}-4-chlorophenyl)methanesulfonamide présatovir N-(2-{[(2S)-2-{5-[(3S)-3-aminopyrrolidin-1-yl]- 6-méthylpyrazolo[1,5-a]pyrimidin-2-yl}pipéridin- 1-yl]carbonyl}-4-chlorophényl)méthanesulfonamide WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 105 presatovir N-(2-{[(2S)-2-{5-[(3S)-3-aminopirrolidin-1-il]- 6-metilpirazolo[1,5-a]pirimidin-2-il}piperidin-1-il]carbonil}- 4-clorofenil)metanosulfonamida C24H30ClN7O3S NH O S CH3 O O N Cl H N N N CH3 N NH2 H rabacfosadinum rabacfosadine diethyl N,N'-[({2-[2-amino-6-(cyclopropylamino)-9H-purin- 9-yl]ethoxy}methyl)phosphinylidene]bis-L-alaninate rabacfosadine N,N'-[({2-[2-amino-6-(cyclopropylamino)-9H-purin- 9-yl]éthoxy}méthyl)phosphinylidène]bis-L-alaninate de diéthyle rabacfosadina N,N'-[({2-[2-amino-6-(ciclopropilamino)-9H-purin- 9-il]etoxi}metil)fosfinilideno]bis-L-alaninato de dietilo C21H35N8O6P N N N N NH O P O NH NH O CH3 O CH3 H2N H3C H H H3C O O rapastinelum rapastinel L-threonyl-L-prolyl-L-prolyl-L-threoninamide rapastinel L-thréonyl-L-prolyl-L-prolyl-L-thréoninamide rapastinel L-treonil-L-prolil-L-prolil-L-treoninamida C18H31N5O6 H2N O H CH3 HO N H O N H O N H O NH2 H CH3HO Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 106 relenopridum relenopride 4-amino-N-[(1-{(3S)-3-[(carbamoyl)oxy]- 3-(4-fluorophenyl)propyl}-piperidin-4-yl)methyl]-5-chloro- 2-methoxybenzamide rélénopride 4-amino-N-[(1-{(3S)-3-[(carbamoyl)oxy]- 3-(4-fluorophényl)propyl}-pipéridin-4-yl)méthyl]-5-chloro- 2-méthoxybenzamide relenoprida 4-amino-N-[(1-{(3S)-3-[(carbamoil)oxi]- 3-(4-fluorofenil)propil}-piperidin-4-il)metil]-5-cloro- 2-metoxibenzamida C24H30ClFN4O4 O N H H2N Cl N OCH3 O H F O NH2 reveglucosidasum alfa # reveglucosidase alfa des-(2-7)-human insulin-like growth factor II fusion protein with glycyl-L-alanyl-L-prolyl-human lysosomal alpha- glucosidase (acid maltase, aglucosidase alfa) produced in Chinese hamster ovary (CHO) cells, glycoform alfa révéglucosidase alfa dès-(2-7)-facteur II de croissance humain semblable à l’insuline, protéine de fusion avec la glycyl-L-alanyl-L-prolyl- alpha-glucosidase lysosomiale humaine (maltase acide, aglucosidase alfa), forme gylcosylée alfa produite par des cellules ovariennes de hamster chinois (CHO) reveglucosidasa alfa des-(2-7)-factor II de crecimiento humano semejante a la insulina, proteína de fusión con la glicil-L-alanil-L-prolil-alfa- glucosidasa lisosómica humana (maltasa ácida, aglucosidasa alfa), forma glicosilada alfa, producida por células ováricas de hamster chino (CHO) C4735H7189N1261O1371S38 Sequence / Séquence / SecuenciaALCGGELVDT LQFVCGDRGF YFSRPASRVS RRSRGIVEEC CFRSCDLALL 50 ETYCATPAKS EGAPAHPGRP RAVPTQCDVP PNSRFDCAPD KAITQEQCEA 100 RGCCYIPAKQ GLQGAQMGQP WCFFPPSYPS YKLENLSSSE MGYTATLTRT 150 TPTFFPKDIL TLRLDVMMET ENRLHFTIKD PANRRYEVPL ETPHVHSRAP 200 SPLYSVEFSE EPFGVIVHRQ LDGRVLLNTT VAPLFFADQF LQLSTSLPSQ 250 YITGLAEHLS PLMLSTSWTR ITLWNRDLAP TPGANLYGSH PFYLALEDGG 300 SAHGVFLLNS NAMDVVLQPS PALSWRSTGG ILDVYIFLGP EPKSVVQQYL 350 DVVGYPFMPP YWGLGFHLCR WGYSSTAITR QVVENMTRAH FPLDVQWNDL 400 DYMDSRRDFT FNKDGFRDFP AMVQELHQGG RRYMMIVDPA ISSSGPAGSY 450 RPYDEGLRRG VFITNETGQP LIGKVWPGST AFPDFTNPTA LAWWEDMVAE 500 FHDQVPFDGM WIDMNEPSNF IRGSEDGCPN NELENPPYVP GVVGGTLQAA 550 TICASSHQFL STHYNLHNLY GLTEAIASHR ALVKARGTRP FVISRSTFAG 600 HGRYAGHWTG DVWSSWEQLA SSVPEILQFN LLGVPLVGAD VCGFLGNTSE 650 ELCVRWTQLG AFYPFMRNHN SLLSLPQEPY SFSEPAQQAM RKALTLRYAL 700 LPHLYTLFHQ AHVAGETVAR PLFLEFPKDS STWTVDHQLL WGEALLITPV 750 LQAGKAEVTG YFPLGTWYDL QTVPIEALGS LPPPPAAPRE PAIHSEGQWV 800 TLPAPLDTIN VHLRAGYIIP LQGPGLTTTE SRQQPMALAV ALTKGGEARG 850 ELFWDDGESL EVLERGAYTQ VIFLARNNTI VNELVRVTSE GAGLQLQKVT 900 VLGVATAPQQ VLSNGVPVSN FTYSPDTKVL DICVSLLMGE QFLVSWC 947 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 3-41 15-54 40-45 77-103 87-104 98-122 528-553 642-653 933-947 Glycosylation sites (N) / Sites de glycosylation (N) / Posiciones de glicosilación (N) Asn-135 Asn-228 Asn-465 Asn-487 Asn-647 Asn-877 Asn-920 WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 107 revusiranum revusiran [(2S,4R)-1-{30-(2-acetamido-2-deoxy- β-D-galactopyranosyl)-14,14-bis[16-(2-acetamido-2-deoxy-β-D- galactopyranosyl)-5,11-dioxo-2,16-dioxa-6,10-diazahexadecyl]- 12,19,25-trioxo-16,30-dioxa-13,20,24-triazatriacontanoyl}-4- hydroxypyrrolidin-2-yl]methyl hydrogen 2'-deoxy-2'- fluorouridylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-deoxy-2'- fluoroguanylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-deoxy-2'- fluoroadenylyl-(3'→5')-2'-O-methyluridylyl-(3'→5')-2'-deoxy-2'- fluorouridylyl-(3'→5')-2'-O-methyluridylyl-(3'→5')-2'-deoxy-2'- fluorocytidylyl-(3'→5')-2'-deoxy-2'-fluoroadenylyl-(3'→5')-2'- deoxy-2'-fluorouridylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'- deoxy-2'-fluorouridylyl-(3'→5')-2'-O-methyladenylyl-(3'→5')-2'- O-methyladenylyl-(3'→5')-2'-O-methylcytidylyl-(3'→5')-2'- deoxy-2'-fluorocytidylyl-(3'→5')-2'-O-methyladenylyl-(3'→5')-2'- deoxy-2'-fluoroadenylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'- deoxy-2'-fluoroadenylate duplex with 2'-O-methyl-P- thiocytidylyl-(5'→3')-2'-deoxy-2'-fluoro-P-thiouridylyl-(5'→3')-2'- O-methyladenylyl-(5'→3')-2'-deoxy-2'-fluorocytidylyl-(5'→3')-2'- O-methylcytidylyl-(5'→3')-2'-deoxy-2'-fluorocytidylyl-(5'→3')-2'- O-methyluridylyl-(5'→3')-2'-deoxy-2'-fluoroadenylyl-(5'→3')-2'- O-methyladenylyl-(5'→3')-2'-deoxy-2'-fluoroadenylyl-(5'→3')-2'- O-methylguanylyl-(5'→3')-2'-O-methyluridylyl-(5'→3')-2'-O- methyladenylyl-(5'→3')-2'-deoxy-2'-fluorocytidylyl-(5'→3')-2'-O- methyladenylyl-(5'→3')-2'-deoxy-2'-fluorouridylyl-(5'→3')-2'- deoxy-2'-fluorouridylyl-(5'→3')-2'-deoxy-2'-fluoroguanylyl- (5'→3')-2'-O-methylguanylyl-(5'→3')-2'-deoxy-2'-fluorouridylyl- (5'→3')-2'-O-methyluridylyl-(5'→3')-2'-deoxy-2'-fluorocytidylyl- (5'→3')-2'-O-methyluridine révusiran duplex de l’hydrogéno-2'-déoxy-2'-fluorouridylyl-(3'→5')-2'-O- méthylguanylyl-(3'→5')-2'-déoxy-2'-fluoroguanylyl-(3'→5')-2'-O- méthylguanylyl-(3'→5')-2'-déoxy-2'-fluoroadénylyl-(3'→5')-2'-O- méthyluridylyl-(3'→5')-2'-déoxy-2'-fluorouridylyl-(3'→5')-2'-O- méthyluridylyl-(3'→5')-2'-déoxy-2'-fluorocytidylyl-(3'→5')-2'- déoxy-2'-fluoroadénylyl-(3'→5')-2'-déoxy-2'-fluorouridylyl- (3'→5')-2'-O-méthylguanylyl-(3'→5')-2'-déoxy-2'-fluorouridylyl- (3'→5')-2'-O-méthyladénylyl-(3'→5')-2'-O-méthyladénylyl- (3'→5')-2'-O-méthylcytidylyl-(3'→5')-2'-déoxy-2'-fluorocytidylyl- (3'→5')-2'-O-méthyladénylyl-(3'→5')-2'-déoxy-2'-fluoroadénylyl- (3'→5')-2'-O-méthylguanylyl-(3'→5')-2'-déoxy-2'- fluoroadénylate de [(2S,4R)-1-{30-(2-acétamido-2-déoxy-β-D- galactopyranosyl)-14,14-bis[16-(2-acétamido-2-déoxy-β-D- galactopyranosyl)-5,11-dioxo-2,16-dioxa-6,10-diazahexadécyl]- 12,19,25-trioxo-16,30-dioxa-13,20,24-triazatriacontanoyl}-4- hydroxypyrrolidin-2-yl]méthyle,avec le 2'-O-méthyl-P- thiocytidylyl-(5'→3')-2'-déoxy-2'-fluoro-P-thiouridylyl-(5'→3')-2'- O-méthyladénylyl-(5'→3')-2'-déoxy-2'-fluorocytidylyl-(5'→3')-2'- O-méthylcytidylyl-(5'→3')-2'-déoxy-2'-fluorocytidylyl-(5'→3')-2'- O-méthyluridylyl-(5'→3')-2'-déoxy-2'-fluoroadénylyl-(5'→3')-2'- O-méthyladénylyl-(5'→3')-2'-déoxy-2'-fluoroadénylyl-(5'→3')-2'- O-méthylguanylyl-(5'→3')-2'-O-méthyluridylyl-(5'→3')-2'-O- méthyladénylyl-(5'→3')-2'-déoxy-2'-fluorocytidylyl-(5'→3')-2'-O- méthyladénylyl-(5'→3')-2'-déoxy-2'-fluorouridylyl-(5'→3')-2'- déoxy-2'-fluorouridylyl-(5'→3')-2'-déoxy-2'-fluoroguanylyl- (5'→3')-2'-O-méthylguanylyl-(5'→3')-2'-déoxy-2'-fluorouridylyl- (5'→3')-2'-O-méthyluridylyl-(5'→3')-2'-déoxy-2'-fluorocytidylyl- (5'→3')-2'-O-méthyluridine Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 108 revusirán dúplex del hidrógeno-2'-desoxi-2'-fluorouridilil-(3'→5')-2'-O- metilguanilil-(3'→5')-2'-desoxi-2'-fluoroguanilil-(3'→5')-2'-O- metilguanilil-(3'→5')-2'-desoxi-2'-fluoroadenilil-(3'→5')-2'-O- metiluridilil-(3'→5')-2'-desoxi-2'-fluorouridilil-(3'→5')-2'-O- metiluridilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')-2'- desoxi-2'-fluoroadenilil-(3'→5')-2'-desoxi-2'-fluorouridilil- (3'→5')-2'-O-metilguanilil-(3'→5')-2'-desoxi-2'-fluorouridilil- (3'→5')-2'-O-metiladenilil-(3'→5')-2'-O-metiladenilil-(3'→5')- 2'-O-metilcitidilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')- 2'-O-metiladenilil-(3'→5')-2'-desoxi-2'-fluoroadenilil-(3'→5')- 2'-O-metilguanilil-(3'→5')-2'-desoxi-2'-fluoroadenilato de [(2S,4R)-1-{30-(2-acetamido-2-desoxi-β-D- galactopiranosil)-14,14-bis[16-(2-acetamido-2-desoxi-β-D- galactopiranosil)-5,11-dioxo-2,16-dioxa-6,10- diazahexadecil]-12,19,25-trioxo-16,30-dioxa-13,20,24- triazatriacontanoil}-4-hidroxipirolidin-2-il]metilo, con el 2'-O-metil-P-tiocitidilil-(5'→3')-2'-desoxi-2'-fluoro-P- tiouridilil-(5'→3')-2'-O-metiladenilil-(5'→3')-2'-desoxi-2'- fluorocitidilil-(5'→3')-2'-O-metilcitidilil-(5'→3')-2'-desoxi-2'- fluorocitidilil-(5'→3')-2'-O-metiluridilil-(5'→3')-2'-desoxi-2'- fluoroadenilil-(5'→3')-2'-O-metiladenilil-(5'→3')-2'-desoxi-2'- fluoroadenilil-(5'→3')-2'-O-metilguanilil-(5'→3')-2'-O- metiluridilil-(5'→3')-2'-O-metiladenilil-(5'→3')-2'-desoxi-2'- fluorocitidilil-(5'→3')-2'-O-metiladenilil-(5'→3')-2'-desoxi-2'- fluorouridilil-(5'→3')-2'-desoxi-2'-fluorouridilil-(5'→3')-2'- desoxi-2'-fluoroguanilil-(5'→3')-2'-O-metilguanilil-(5'→3')-2'- desoxi-2'-fluorouridilil-(5'→3')-2'-O-metiluridilil-(5'→3')-2'- desoxi-2'-fluorocitidilil-(5'→3')-2'-O-metiluridina C517H676F22N171O314P43S2 [(3’-5’) U-G-G-G-A-U-U-U-C-A-U-G-U-A-A-C-C-A-A-G-A-R1] . . . . . . . . . . . . . . . . . . . [(5’-3’) Cs-Us-A-C-C-C-U-A-A-A-G-U-A-C-A-U-U-G-G-U-U-C-U] Legend X = 2'-deoxy-2'-fluoro X = 2'-O-methyl - = -PO2H- s- = -POSH- N O H N O R R R H O H O O OH HO N H HO H N H N CH3 O O O ribociclibum ribociclib 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin- 2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide ribociclib 7-cyclopentyl-N,N-diméthyl-2-{[5-(pipérazin-1-yl)pyridin- 2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide ribociclib 7-ciclopentil-N,N-dimetil-2-{[5-(piperazin-1-il)piridin- 2-il]amino}-7H-pirrolo[2,3-d]pirimidina-6-carboxamida WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 109 C23H30N8O N N NN H N O H3C CH3N N HN rimiducidum rimiducid 1,1'-{ethane-1,2-diylbis[azanediyl(2-oxoethan-2,1-diyl)oxy- 3,1-phenylene]bis[(1R)-3-(3,4-dimethoxyphenyl)propyl] bis{(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]- piperidine-2-carboxylate} rimiducid bis{(2S)-1-[(2S)-2-(3,4,5- triméthoxyphényl)butanoyl]pipéridine-2-carboxylate} de 1,1'-{éthane-1,2-diylbis[azanediyl(2-oxoéthan-2,1-diyl)oxy- 3,1-phénylène]bis[(1R)-3-(3,4-diméthoxyphényl)propyl] rimiducid bis{(2S)-1-[(2S)-2-(3,4,5-trimetoxifenil)butanoil]piperidina- 2-carboxilato} de 1,1'-{etano-1,2-diilbis[azanodiil(2- oxoetan-2,1-diil)oxi-3,1-fenileno]bis[(1R)-3-(3,4- dimetoxifenil)propil] C78H98N4O20 O O O N O OCH3 OCH3 H3CO H H3C H H OO N O H3CO OCH3 OCH3 H CH3H H OCH3 H3CO OCH3 OCH3 N H O NH O O rociletinibum rociletinib N-[3-({2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]- 5-(trifluoromethyl)pyrimidin-4-yl}amino)phenyl]prop- 2-enamide rocilétinib N-[3-({2-[4-(4-acétylpipérazin-1-yl)-2-méthoxyanilino]- 5-(trifluorométhyl)pyrimidin-4-yl}amino)phényl]prop- 2-énamide Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 110 rociletinib N-[3-({2-[4-(4-acetilpiperazin-1-il)-2-metoxianilino]- 5-(trifluorometil)pirimidin-4-il}amino)fenil]prop-2-enamida C27H28F3N7O3 N N N H N H F3C NH O O CH3 H2C N N CH3 O rurioctocogum alfa pegolum # rurioctocog alfa pegol pegylated recombinant DNA derived human blood coagulation factor VIII, produced in Chinese hamster ovary (CHO cells), glycoform alfa: human blood coagulation factor VIII (antihemophilic factor, procoagulant component)-(1-1648)-peptide associated to (1649-2332)-peptide, glycoform alfa produced in CHO cells, some of its lysine residues are N6 substituted with 4-[1,3-bis({[α- methylpoly(oxyethylene)]carbamoyl}oxy)propan- 2-yloxy]butanoyl radicals rurioctocog alfa pégol facteur VIII de coagulation humain, produit par des cellules ovariennes de hamster chinois à partir d'ADN recombinant, pégylé, forme glycosylée alfa; association des peptides (1-1648)- et (1649-2332)- du facteur VIII de coagulation humain (facteur antihémophilique, composé procoagulant) produite par des cellules ovariennes de hamster chinois sous forme glycosylée alfa dont quelques résidus lysine sont N6 substitués par le radical 4-[1,3-bis({[α- méthylpoly(oxyéthylène)]carbamoyl}oxy)propan- 2-yloxy]butanoyle rurioctocog alfa pegol factor VIII de coagulación humano, producido por células ováricas de hamster chino a partir de ADN recombinante, pegilado, forma glicosilada alfa; asociación de péptidos (1-1648)- y (1649-2332)- del factor VIII de coagulación humano (factor antihémofílico, componente procoagulante) producido por células ováricas de hamster chino en forma glicosilada alfa algunos de cuyos restos lisina están N6 substituidos por radicales 4-[1,3-bis({[α- metilpoli(oxietileno)]carbamoil}oxi)propan-2-iloxi]butanoilo WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 111 O O H N OH3C n n O H N O CH3 O O C O n # 230 = R CO2H NH2H O S HO O O H2N CO2H HNHR * potential pegylated residues / résidus pouvant être pégylés / restos potencialmente pegilados Glycosylation sites (N) / Sites de glycosylation (N) / Posiciones de glicosilación (N) Asn-41 Asn-239 Asn-582 Asn-757 Asn-784 Asn-828 Asn-900 Asn-943 Asn-963 Asn-1001 Asn-1005 Asn-1055 Asn-1066 Asn-1185 Asn-1255 Asn-1259 Asn-1282 Asn-1300 Asn-1412 Asn-1442 Asn-1810 Asn-2118 K* Y 346-718-719-723-1664-1680 O-sulfoTyr Heavy chain / Chaîne lourde / Cadena pesada ATRRYYLGAV ELSWDYMQSD LGELPVDARF PPRVPKSFPF NTSVVYKKTL 50 FVEFTDHLFN IAKPRPPWMG LLGPTIQAEV YDTVVITLKN MASHPVSLHA 100 VGVSYWKASE GAEYDDQTSQ REKEDDKVFP GGSHTYVWQV LKENGPMASD 150 PLCLTYSYLS HVDLVKDLNS GLIGALLVCR EGSLAKEKTQ TLHKFILLFA 200 VFDEGKSWHS ETKNSLMQDR DAASARAWPK MHTVNGYVNR SLPGLIGCHR 250 KSVYWHVIGM GTTPEVHSIF LEGHTFLVRN HRQASLEISP ITFLTAQTLL 300 MDLGQFLLFC HISSHQHDGM EAYVKVDSCP EEPQLRMKNN EEAEDYDDDL 350 TDSEMDVVRF DDDNSPSFIQ IRSVAKKHPK TWVHYIAAEE EDWDYAPLVL 400 APDDRSYKSQ YLNNGPQRIG RKYKKVRFMA YTDETFKTRE AIQHESGILG 450 PLLYGEVGDT LLIIFKNQAS RPYNIYPHGI TDVRPLYSRR LPKGVKHLKD 500 FPILPGEIFK YKWTVTVEDG PTKSDPRCLT RYYSSFVNME RDLASGLIGP 550 LLICYKESVD QRGNQIMSDK RNVILFSVFD ENRSWYLTEN IQRFLPNPAG 600 VQLEDPEFQA SNIMHSINGY VFDSLQLSVC LHEVAYWYIL SIGAQTDFLS 650 VFFSGYTFKH KMVYEDTLTL FPFSGETVFM SMENPGLWIL GCHNSDFRNR 700 GMTALLKVSS CDKNTGDYYE DSYEDISAYL LSKNNAIEPR SFSQNSRHPS 750 TRQKQFNATT IPENDIEKTD PWFAHRTPMP KIQNVSSSDL LMLLRQSPTP 800 HGLSLSDLQE AKYETFSDDP SPGAIDSNNS LSEMTHFRPQ LHHSGDMVFT 850 PESGLQLRLN EKLGTTAATE LKKLDFKVSS TSNNLISTIP SDNLAAGTDN 900 TSSLGPPSMP VHYDSQLDTT LFGKKSSPLT ESGGPLSLSE ENNDSKLLES 950 GLMNSQESSW GKNVSSTESG RLFKGKRAHG PALLTKDNAL FKVSISLLKT 1000 NKTSNNSATN RKTHIDGPSL LIENSPSVWQ NILESDTEFK KVTPLIHDRM 1050 LMDKNATALR LNHMSNKTTS SKNMEMVQQK KEGPIPPDAQ NPDMSFFKML 1100 FLPESARWIQ RTHGKNSLNS GQGPSPKQLV SLGPEKSVEG QNFLSEKNKV 1150 VVGKGEFTKD VGLKEMVFPS SRNLFLTNLD NLHENNTHNQ EKKIQEEIEK 1200 KETLIQENVV LPQIHTVTGT KNFMKNLFLL STRQNVEGSY DGAYAPVLQD 1250 FRSLNDSTNR TKKHTAHFSK KGEEENLEGL GNQTKQIVEK YACTTRISPN 1300 TSQQNFVTQR SKRALKQFRL PLEETELEKR IIVDDTSTQW SKNMKHLTPS 1350 TLTQIDYNEK EKGAITQSPL SDCLTRSHSI PQANRSPLPI AKVSSFPSIR 1400 PIYLTRVLFQ DNSSHLPAAS YRKKDSGVQE SSHFLQGAKK NNLSLAILTL 1450 EMTGDQREVG SLGTSATNSV TYKKVENTVL PKPDLPKTSG KVELLPKVHI 1500 YQKDLFPTET SNGSPGHLDL VEGSLLQGTE GAIKWNEANR PGKVPFLRVA 1550 TESSAKTPSK LLDPLAWDNH YGTQIPKEEW KSQEKSPEKT AFKKKDTILS 1600 LNACESNHAI AAINEGQNKP EIEVTWAKQG RTERLCSQNP PVLKRHQR 1648 Light chain / Chaîne légère / Cadena ligera EI 1650 TRTTLQSDQE EIDYDDTISV EMKKEDFDIY DEDENQSPRS FQKKTRHYFI 1700 AAVERLWDYG MSSSPHVLRN RAQSGSVPQF KKVVFQEFTD GSFTQPLYRG 1750 ELNEHLGLLG PYIRAEVEDN IMVTFRNQAS RPYSFYSSLI SYEEDQRQGA 1800 EPRKNFVKPN ETKTYFWKVQ HHMAPTKDEF DCKAWAYFSD VDLEKDVHSG 1850 LIGPLLVCHT NTLNPAHGRQ VTVQEFALFF TIFDETKSWY FTENMERNCR 1900 APCNIQMEDP TFKENYRFHA INGYIMDTLP GLVMAQDQRI RWYLLSMGSN 1950 ENIHSIHFSG HVFTVRKKEE YKMALYNLYP GVFETVEMLP SKAGIWRVEC 2000 LIGEHLHAGM STLFLVYSNK CQTPLGMASG HIRDFQITAS GQYGQWAPKL 2050 ARLHYSGSIN AWSTKEPFSW IKVDLLAPMI IHGIKTQGAR QKFSSLYISQ 2100 FIIMYSLDGK KWQTYRGNST GTLMVFFGNV DSSGIKHNIF NPPIIARYIR 2150 LHPTHYSIRS TLRMELMGCD LNSCSMPLGM ESKAISDAQI TASSYFTNMF 2200 ATWSPSKARL HLQGRSNAWR PQVNNPKEWL QVDFQKTMKV TGVTTQGVKS 2250 LLTSMYVKEF LISSSQDGHQ WTLFFQNGKV KVFQGNQDSF TPVVNSLDPP 2300 LLTRYLRIHP QSWVHQIALR MEVLGCEAQD LY 2332 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 153-179 248-329 528-554 630-711 1832-1858 1899-1903 2021-2169 2174-2326 Modified residues / Résidus modifiés / Restos modificados sarolanerum sarolaner 1-{5'-[(5S)-5-(3,5-dichloro-4-fluorophenyl)- 5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl]- 3'-H-spiro[azetidine-3,1'-[2]benzofuran]-1-yl}- 2-(methanesulfonyl)ethanone sarolaner 1-{5'-[(5S)-5-(3,5-dichloro-4-fluorophényl)- 5-(trifluorométhyl)-4,5-dihydroisoxazol-3-yl]- 3'-H-spiro[azétidine-3,1'-[2]benzofuran]-1-yl}- 2-(méthanesulfonyl)éthanone Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 112 sarolaner 1-{5'-[(5S)-5-(3,5-dicloro-4-fluorofenil)-5-(trifluorometil)- 4,5-dihidroisoxazol-3-il]-3'-H-espiro[azetidina- 3,1'-[2]benzofuran]-1-il}-2-(metilsulfonil)etanona C23H18Cl2F4N2O5S NOF3C Cl Cl F O N O S CH3 OO savolitinibum savolitinib 1-[(1S)-1-(imidazo[1,2-a]pyridin-6-yl)ethyl]-6-(1-methyl- 1H-pyrazol-4-yl)-1H-1,2,3-triazolo[4,5-b]pyrazine savolitinib 1-[(1S)-1-(imidazo[1,2-a]pyridin-6-yl)éthyl]-6-(1-méthyl- 1H-pyrazol-4-yl)-1H-1,2,3-triazolo[4,5-b]pyrazine savolitinib 1-[(1S)-1-(imidazo[1,2-a]piridin-6-il)etil]-6-(1-metil- 1H-pirazol-4-il)-1H-1,2,3-triazolo[4,5-b]pirazina C17H15N9 N N N N N N NN NH3C H H3C sembragilinum sembragiline N-[(3S)-1-{4-[(3-fluorophenyl)methoxy]phenyl}- 5-oxopyrrolidin-3-yl]acetamide sembragiline N-[(3S)-1-{4-[(3-fluorophényl)méthoxy]phényl}- 5-oxopyrrolidin-3-yl]acétamide sembragilina N-[(3S)-1-{4-[(3-fluorofenil)metoxi]fenil}-5-oxopirrolidin- 3-il]acetamida C19H19FN2O3 F O N N H H O CH3 O tenofovirum alafenamidum tenofovir alafenamide propan-2-yl N-[(S)-({[(2R)-1-(6-amino-9H-purin- 9-yl)propan-2-yl]oxy}methyl)phenoxyphosphinoyl]- L-alaninate WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 113 ténofovir alafénamide N-[(S)-({[(2R)-1-(6-amino-9H-purin-9-yl)propan- 2-yl]oxy}méthyl)phénoxyphosphinoyl]-L-alaninate de propan-2-yle tenofovir alafenamida N-[(S)-({[(2R)-1-(6-amino-9H-purin-9-il)propan- 2-il]oxi}metil)fenoxifosfinoil]-L-alaninato de propan-2-ilo C21H29N6O5P N N N N NH2 O P O O H N CH3 H O O CH3 CH3 CH3 H tepotinibum tepotinib 3-{1-[(3-{5-[(1-methylpiperidin-4-yl)methoxy]pyrimidin- 2-yl}phenyl)methyl]-6-oxo-1,6-dihydropyridazin- 3-yl}benzonitrile tépotinib 3-{1-[(3-{5-[(1-méthylpipéridin-4-yl)méthoxy]pyrimidin- 2-yl}phényl)méthyl]-6-oxo-1,6-dihydropyridazin- 3-yl}benzonitrile tepotinib 3-{1-[(3-{5-[(1-metilpiperidin-4-il)metoxi]pirimidin- 2-il}fenil)metil]-6-oxo-1,6-dihidropiridazin-3-il}benzonitrilo C29H28N6O2 N H3C O N N N N O CN tradipitantum tradipitant {2-[1-{[3,5-bis(trifluoromethyl)phenyl]methyl}-5-(pyridin- 4-yl)-1H-1,2,3-triazol-4-yl]pyridin-3-yl}(2- chlorophenyl)methanone tradipitant {2-[1-{[3,5-bis(trifluorométhyl)phényl]méthyl}-5-(pyridin- 4-yl)-1H-1,2,3-triazol-4-yl]pyridin-3-yl}(2- chlorophényl)méthanone tradipitant {2-[1-{[3,5-bis(trifluorometil)fenil]metil}-5-(piridin-4-il)- 1H-1,2,3-triazol-4-il]piridin-3-il}(2-clorofenil)metanona Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 114 C28H16ClF6N5O N N N N O CF3 CF3Cl N transcrocetinum transcrocetin all-trans-8,8'-diapocarotene-8,8'-dioic acid transcrocétine acide tout-trans-8,8'-diapocarotène-8,8'-dioïque transcrocetina ácido todo-trans-8,8'-diapocaroteno-8,8'-dioico C20H24O4 CH3 CH3 CH3 CH3 CO2H HO2C ulixertinibum ulixertinib 4-{5-chloro-2-[(propan-2-yl)amino]pyridin-4-yl}- N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole- 2-carboxamide ulixertinib 4-{5-chloro-2-[(propan-2-yl)amino]pyridin-4-yl}- N-[(1S)-1-(3-chlorophényl)-2-hydroxyéthyl]-1H-pyrrole- 2-carboxamide ulixertinib 4-{5-cloro-2-[(propan-2-il)amino]piridin-4-il}- N-[(1S)-1-(3-clorofenil)-2-hidroxietil]-1H-pirrol- 2-carboxamida C21H22Cl2N4O2 N HN CH3 H3C Cl H N O N H H OH Cl WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 115 uprosertibum uprosertib N-[(2S)-1-amino-3-(3,4-difluorophenyl)propan-2-yl]- 5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)furan- 2-carboxamide uprosertib N-[(2S)-1-amino-3-(3,4-difluorophényl)propan-2-yl]- 5-chloro-4-(4-chloro-1-méthyl-1H-pyrazol-5-yl)furan- 2-carboxamide uprosertib N-[(2S)-1-amino-3-(3,4-difluorofenil)propan-2-il]-5-cloro- 4-(4-cloro-1-metil-1H-pirazol-5-il)furan-2-carboxamida C18H16Cl2F2N4O2 O H N H F NH2 O Cl N N CH3 Cl F vanucizumabum # vanucizumab immunoglobulin recombined G1-kappa/lambda, anti-[Homo sapiens ANGPT2 (angiopoietin 2, Ang2)]/anti-Homo sapiens VEGFA (vascular endothelial growth factor A, VEGF-A, VEGF)], humanized monoclonal antibody; gamma1 heavy chain anti-ANGPT2 (1-463) [Homo sapiens VH (Homo sapiens IGHV1-2*02 (100.00%) -(IGHD)- IGHJ3*02) [8.8.22] (1-129) -Homo sapiens IGKC*01 R1.4>A (130), T1.3>S (131) (130-236) -IGHG1*01 hinge- CH2-CH3-CHS (hinge 6-15 (237-246), CH2 (247-356), CH3 Y5>C (365), T22>S (382), L24>A (384), Y86>V (423) (357-461), CHS (462-463)) (237-463)], (236-213')-disulfide with light chain anti-ANGPT2 (1’-213’) [glutaminyl-prolyl- glycyl (1’-3’) -Homo sapiens V-LAMBDA (Homo sapiens IGLV3-21*02 (100.00%) -IGLJ1*01) [6.3.11] (4'-108') - linker seryl-seryl (109’-110’) -Homo sapiens IGHG1*01 CH1-hinge (CH1 (111'-208') -hinge (1-5) (209’-213’)]; gamma1 heavy chain anti-VEGFA (1-453) [humanized VH (Homo sapiens IGHV3-23*03 (76.80%) -(IGHD)-IGHJ4*01) [8.8.16] (1-123) -Homo sapiens IGHG1*01 (CH1 (124- 221), hinge (222-236), CH2 (237-346), CH3 S10>C (360), T22>W (372) (347-451), CHS (452-453)) (124-453)],(226- 214')-disulfide with kappa light chain anti-VEGFA (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV1-16*01 (88.40%) -IGKJ1*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01 (108'-214')]; dimer (242-232":245-235":365-360")- trisdisulfide Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 116 vanucizumab immunoglobuline recombinée G1-kappa/lambda, anti- [Homo sapiens ANGPT2 (angiopoietine 2, Ang2)]/anti- Homo sapiens VEGFA (facteur de croissance A de l’endothélium vasculaire, VEGF-A, VEGF)], anticorps monoclonal humanisé; chaîne lourde gamma1 anti-ANGPT2 (1-463) [Homo sapiens VH (Homo sapiens IGHV1-2*02 (100.00%) - (IGHD)-IGHJ3*02) [8.8.22] (1-129) -Homo sapiens IGKC*01 R1.4>A (130), T1.3>S (131) (130-236) - IGHG1*01 charnière-CH2-CH3-CHS (charnière 6-15 (237- 246), CH2 (247-356), CH3 Y5>C (365), T22>S (382), L24>A (384), Y86>V (423) (357-461), CHS (462-463)) (237-463)], (236-213')-disulfure avec la chaîne légère anti- ANGPT2 (1’-213’) [glutaminyl-prolyl-glycyl (1’-3’) -Homo sapiens V-LAMBDA (Homo sapiens IGLV3-21*02 (100.00%) -IGLJ1*01) [6.3.11] (4'-108') -linker séryl-séryl (109’-110’) -Homo sapiens IGHG1*01 CH1-charnière (CH1 (111'-208') -charnière (1-5) (209’-213’)]; chaîne lourde gamma1 anti-VEGFA (1-453) [VH humanisé (Homo sapiens IGHV3-23*03 (76.80%) -(IGHD)-IGHJ4*01) [8.8.16] (1-123) -Homo sapiens IGHG1*01 (CH1 (124- 221), charnière (222-236), CH2 (237-346), CH3 S10>C (360) T22>W (372) (347-451), CHS (452-453)) (124- 453)],(226-214')-disulfure avec la chaîne légère kappa anti- VEGFA (1’-214’) [V-KAPPA humanisé (Homo sapiens IGKV1-16*01 (88.40%) -IGKJ1*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01 (108'-214')]; dimère (242-232":245- 235":365-360")-trisdisulfure vanucizumab inmunoglobulina recombinada G1-kappa/lambda, anti- [Homo sapiens ANGPT2 (angiopoyetina 2, Ang2)]/anti- Homo sapiens VEGFA (factor de crecimiento A del endotelio vascular, VEGF-A, VEGF)], anticuerpo monoclonal humanizado; cadena pesada gamma1 anti-ANGPT2 (1-463) [Homo sapiens VH (Homo sapiens IGHV1-2*02 (100.00%) - (IGHD)-IGHJ3*02) [8.8.22] (1-129) -Homo sapiens IGKC*01 R1.4>A (130), T1.3>S (131) (130-236) - IGHG1*01 bisagra-CH2-CH3-CHS (bisagra 6-15 (237- 246), CH2 (247-356), CH3 Y5>C (365), T22>S (382), L24>A (384), Y86>V (423) (357-461), CHS (462-463)) (237-463)], (236-213')-disulfuro con la cadena ligera anti- ANGPT2 (1’-213’) [glutaminil-prolil-glicil (1’-3’) -Homo sapiens V-LAMBDA (Homo sapiens IGLV3-21*02 (100.00%) -IGLJ1*01) [6.3.11] (4'-108') –conector seril-seril (109’-110’) -Homo sapiens IGHG1*01 CH1-bisagra (CH1 (111'-208') -bisagra (1-5) (209’-213’)]; cadena pesada gamma1 anti-VEGFA (1-453) [VH humanizado (Homo sapiens IGHV3-23*03 (76.80%) - (IGHD)-IGHJ4*01) [8.8.16] (1-123) -Homo sapiens IGHG1*01 (CH1 (124-221), bisagra (222-236), CH2 (237- 346), CH3 S10>C (360) T22>W (372) (347-451), CHS (452-453)) (124-453)], (226-214')-disulfuro con la cadena ligera kappa anti-VEGFA (1’-214’) [V-KAPPA humanizado (Homo sapiens IGKV1-16*01 (88.40%) -IGKJ1*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01 (108'-214')]; dímero (242-232":245-235":365-360")-trisdisulfuro WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 117 anti- ANGPT2 Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGW 50 INPNSGGTNY AQKFQGRVTM TRDTSISTAY MELSRLRSDD TAVYYCARSP 100 NPYYYDSSGY YYPGAFDIWG QGTMVTVSSA SVAAPSVFIF PPSDEQLKSG 150 TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 200 LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGECDKTH TCPPCPAPEL 250 LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV 300 HNAKTKPREE QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK 350 TISKAKGQPR EPQVCTLPPS RDELTKNQVS LSCAVKGFYP SDIAVEWESN 400 GQPENNYKTT PPVLDSDGSF FLVSKLTVDK SRWQQGNVFS CSVMHEALHN 450 HYTQKSLSLS PGK 463 anti- ANGPT2 Light chain / Chaîne légère / Cadena ligera QPGLTQPPSV SVAPGQTARI TCGGNNIGSK SVHWYQQKPG QAPVLVVYDD 50 SDRPSGIPER FSGSNSGNTA TLTISRVEAG DEADYYCQVW DSSSDHYVFG 100 TGTKVTVLSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS 150 WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS 200 NTKVDKKVEP KSC 213 anti-VEGFA Heavy chain / Chaîne lourde / Cadena pesada EVQLVESGGG LVQPGGSLRL SCAASGYTFT NYGMNWVRQA PGKGLEWVGW 50 INTYTGEPTY AADFKRRFTF SLDTSKSTAY LQMNSLRAED TAVYYCAKYP 100 HYYGSSHWYF DVWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC 150 LVKDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG 200 TQTYICNVNH KPSNTKVDKK VEPKSCDKTH TCPPCPAPEL LGGPSVFLFP 250 PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300 QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR 350 EPQVYTLPPC RDELTKNQVS LWCLVKGFYP SDIAVEWESN GQPENNYKTT 400 PPVLDSDGSF FLYSKLTVDK SRWQQGNVFS CSVMHEALHN HYTQKSLSLS 450 PGK 453 anti-VEGFA Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCSASQDIS NYLNWYQQKP GKAPKVLIYF 50 TSSLHSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ YSTVPWTFGQ 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 156-216 277-337 383-441 22''-96'' 150''-206'' 267''-327'' 373''-431'' Intra-L (C23-C104) 22'-87' 137'-193' 23'''-88''' 134'''-194''' Inter-H-L 236-213' 226''-214''' Inter-H-H 242-232'' 245-235'' 365-360'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 313, 303'' varlilumabum # varlilumab immunoglobulin G1-kappa, anti-[Homo sapiens anti-CD27 (TNFRSF7, tumor necrosis factor receptor superfamily member 7)], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-452)[Homo sapiens VH (IGHV3- 33*01 (99.00%) -(IGHD)-IGHJ4*01) [8.8.12](1-119) - IGHG1*01 (CH1 (120-217), hinge (218-232), CH2 (233- 342), CH3 (343-447), CHS (448-449) (120-449) -glycyl- seryl-seryl (450-452)],(222-214')-disulfide with kappa light chain (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (97.90%) -IGKJ1*01) [6.3.9] (1'-107') -IGKC*01 (108'- 214')]; dimer (228-228'':231-231'')-bisdisulfide varlilumab immunoglobuline G1-kappa, anti-[Homo sapiens anti-CD27 (TNFRSF7, membre 7 de la superfamille des récepteurs du facteur de nécrose tumorale)], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-452)[Homo sapiens VH (IGHV3- 33*01 (99.00%) -(IGHD)-IGHJ4*01) [8.8.12](1-119) - IGHG1*01 (CH1 (120-217), charnière (218-232), CH2 (233-342), CH3 (343-447), CHS (448-449) (120-449) - glycyl-séryl-séryl (450-452)], (222-214')-disulfure avec la chaîne légère kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (97.90%) -IGKJ1*01) [6.3.9] (1'-107') - IGKC*01 (108'-214')]; dimère (228-228'':231-231'')- bisdisulfure Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 118 varlilumab inmunoglobulina G1-kappa, anti-[Homo sapiens anti-CD27 (TNFRSF7, miembro 7 de la superfamilia de receptores del factor de necrosis tumoral)] anticuerpo monoclonal de Homo sapiens; cadena pesada gamma1 (1-452) [Homo sapiens VH (IGHV3-33*01 (99.00%) -(IGHD)-IGHJ4*01) [8.8.12] (1- 119) -IGHG1*01 (CH1 (120-217), bisagra (218-232), CH2 (233-342), CH3 (343-447), CHS (448-449) (120-449) - glicil-seril-seril (450-452)], (222-214')-disulfuro con la cadena ligera kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (97.90%) -IGKJ1*01) [6.3.9] (1'-107') - IGKC*01 (108'-214')]; dímero (228-228'':231-231'')- bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVESGGG VVQPGRSLRL SCAASGFTFS SYDMHWVRQA PGKGLEWVAV 50 IWYDGSNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARGS 100 GNWGFFDYWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD 150 YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY 200 ICNVNHKPSN TKVDKKVEPK SCDKTHTCPP CPAPELLGGP SVFLFPPKPK 250 DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS 300 TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL PAPIEKTISK AKGQPREPQV 350 YTLPPSRDEL TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 400 DSDGSFFLYS KLTVDKSRWQ QGNVFSCSVM HEALHNHYTQ KSLSLSPGKG 450 SS 452 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCRASQGIS RWLAWYQQKP EKAPKSLIYA 50 ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ YNTYPRTFGQ 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 146-202 263-323 369-427 22''-96'' 146''-202'' 263''-323'' 369''-427'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 222-214' 222''-214''' Inter-H-H (h 11, h 14) 228-228'' 231-231'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 299, 299'' velpatasvirum velpatasvir methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2- [(methoxycarbonyl)amino]-2-phenylacetyl}- 4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-4-yl}- 1,11-dihydro[2]benzopyrano[4',3':6,7]naphtho[1,2- d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl- 1-oxobutan-2-yl}carbamate velpatasvir {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2- [(méthoxycarbonyl)amino]-2-phénylacétyl}- 4-(méthoxyméthyl)pyrrolidin-2-yl]-1H-imidazol-4-yl}- 1,11-dihydro[2]benzopyrano[4',3':6,7]naphtho[1,2- d]imidazol-2-yl)-5-méthylpyrrolidin-1-yl]-3-méthyl- 1-oxobutan-2-yl}carbamate de méthyle velpatasvir {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2- [(metoxicarbonil)amino]-2-fenilacetil}- 4-(metoximetil)pirrolidin-2-il]-1H-imidazol-4-il}- 1,11-dihidro[2]benzopirano[4',3':6,7]nafto[1,2-d]imidazol- 2-il)-5-metilpirrolidin-1-il]-3-metil-1-oxobutan-2-il}carbamato de metilo WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 119 C49H54N8O8 O N HN N HN N O NH O O CH3 H N H H CH3 CH3 CH3 H H O H3C HN O O CH3 O H venetoclaxum venetoclax 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en- 1-yl]methyl}piperazin-1-yl)-N-[(3-nitro-4-{[(oxan- 4-yl)methyl]amino}phenyl)sulfonyl]-2-[(1H-pyrrolo[2,3- b]pyridin-5-yl)oxy]benzamide vénétoclax 4-(4-{[2-(4-chlorophényl)-4,4-diméthylcyclohex-1-én- 1-yl]méthyl}pipérazin-1-yl)-N-[(3-nitro-4-{[(oxan- 4-yl)méthyl]amino}phényl)sulfonyl]-2-[(1H-pyrrolo[2,3- b]pyridin-5-yl)oxy]benzamide venetoclax 4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en- 1-il]metil}piperazin-1-il)-N-[(3-nitro-4-{[(oxan- 4-il)metil]amino}fenil)sulfonil]-2-[(1H-pirrolo[2,3-b]piridin- 5-il)oxi]benzamida C45H50ClN7O7S N O N H S NO2 NH N Cl OO O N NH H3C H3C O verinuradum verinurad 2-{[3-(4-cyanonaphthalen-1-yl)pyridin-4-yl]sulfanyl}- 2-methylpropanoic acid vérinurad acide 2-{[3-(4-cyanonaphtalén-1-yl)pyridin-4-yl]sulfanyl}- 2-méthylpropanoïque verinurad ácido 2-{[3-(4-cianonaftalen-1-il)piridin-4-il]sulfanil}- 2-metilpropanoico Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 120 C20H16N2O2S NC N S CO2H H3C CH3 vonapanitasum vonapanitase recombinant DNA derived type I pancreatic elastase, produced in Pichia pastoris: [26-tryptophan(Arg>Trp),202-leucine(Val>Leu),225- arginine(Gln>Arg)]mature human CELA1 (chymotrypsin- like elastase family member 1, pancreatic elastase 1, elastase 1, EC 3.4.21.36) non-glycosylated vonapanitase élastase pancréatique de type I, produite à partir d'ADN recombinant, produite par Pichia pastoris: [26-tryptophane(Arg>Trp),202-leucine(Val>Leu),225- arginine(Gln>Arg)]CELA1 humaine à maturité (membre 1 de la famille des élastases analogues de la chymotrypsine, élastase 1 pancréatique, élastase 1, EC 3.4.21.36) non- glycosylée vonapanitasa elastasa pancreática de tipo I, producida a partir de ADN recombinante, producida por Pichia pastoris: [26-triptófano(Arg>Trp),202-leucina(Val>Leu),225- arginina(Gln>Arg)]CELA1 humana madura (miembro 1 de la familia de elastasas análogas a la quimotripsina, elastasa 1 pancreática, elastasa 1, EC 3.4.21.36) no glicosilada Sequence / Séquence / SecuenciaVVGGTEAGRN SWPSQISLQY RSGGSWYHTC GGTLIRQNWV MTAAHCVDYQ 50 KTFRVVAGDH NLSQNDGTEQ YVSVQKIVVH PYWNSDNVAA GYDIALLRLA 100 QSVTLNSYVQ LGVLPQEGAI LANNSPCYIT GWGKTKTNGQ LAQTLQQAYL 150 PSVDYAICSS SSYWGSTVKN TMVCAGGDGV RSGCQGDSGG PLHCLVNGKY 200 SLHGVTSFVS SRGCNVSRKP TVFTRVSAYI SWINNVIASN 240 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 30-46 127-194 158-174 184-214 vorhyaluronidasum alfa # vorhyaluronidase alfa human hyaluronidase PH-20 (hyaluronoglucosaminidase PH-20, sperm adhesion molecule 1, EC 3.2.1.35) precursor-(36-482)-peptide (mature-(1-447)-peptide), produced in Chinese hamster ovary (CHO) DG44dhfr- cells, glycoform alfa vorhyaluronidase alfa hyaluronidase PH-20 humaine (hyaluronoglucosaminidase PH-20, molécule adhésive 1 du sperme, EC 3.2.1.35) précurseur-(36-482)-peptide (à maturité-(1-447)-peptide), produite par des cellules ovariennes de hamster chinois DG44dhfr-, forme glycosylée alfa WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 121 vorhialuronidasa alfa hialuronidasa PH-20 humana (hialuronoglucosaminidasa PH-20, molécula de adhesión 1 de esperma, EC 3.2.1.35) precursor-(36-482)-péptido (maduro-(1-447)-péptido), producida por células ováricas de hamster chino DG44dhfr-, forma glicosilada alfa C2327H3553N589O667S20 (protein) Sequence / Séquence / SecuenciaLNFRAPPVIP NVPFLWAWNA PSEFCLGKFD EPLDMSLFSF IGSPRINATG 50 QGVTIFYVDR LGYYPYIDSI TGVTVNGGIP QKISLQDHLD KAKKDITFYM 100 PVDNLGMAVI DWEEWRPTWA RNWKPKDVYK NRSIELVQQQ NVQLSLTEAT 150 EKAKQEFEKA GKDFLVETIK LGKLLRPNHL WGYYLFPDCY NHHYKKPGYN 200 GSCFNVEIKR NDDLSWLWNE STALYPSIYL NTQQSPVAAT LYVRNRVREA 250 IRVSKIPDAK SPLPVFAYTR IVFTDQVLKF LSQDELVYTF GETVALGASG 300 IVIWGTLSIM RSMKSCLLLD NYMETILNPY IINVTLAAKM CSQVLCQEQG 350 VCIRKNWNSS DYLHLNPDNF AIQLEKGGKF TVRGKPTLED LEQFSEKFYC 400 SCYSTLSCKE KADVKDTDAV DVCIADGVCI DAFLKPPMET EEPQIFY 447 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 25-316 189-203 341-352 346-400 402-408 423-429 Glycosylation sites (N, T) / Sites de glycosylation (N, T) / Posiciones de glicosilación (N, T) Asn-47 Asn-131 Asn-200 Asn-219 Asn-333 Asn-358 Thr-440 AMENDMENTS TO PREVIOUS LISTS MODIFICATIONS APPORTÉES AUX LISTES ANTÉRIEURES MODIFICACIONES A LAS LISTAS ANTERIORES Recommended International Non Proprietary Names (Rec. INN): List 57 Dénominations communes internationales proposées (DCI Rec.): Liste 57 Denominaciones Comunes Internacionales Propuestas (DCI Rec.): Lista 57 (WHO Drug Information, Vol. 21, No. 1, 2007) p. 60 beroctocogum alfa # beroctocog alfa replace the description by the following one béroctocog alfa remplacer la description par la suivante beroctocog alfa sustitúyase la descripción por la siguiente human blood-coagulation factor VIII-(1-741)-peptide complex with human blood-coagulation factor VIII-(1649-2332)-peptide combinaison du facteur VIII de coagulation humain-(1-741)-peptide avec le facteur VIII de coagulation humain-(1649-2332)-peptide combinación del factor VIII de coagulación humano-(1-741)-péptido con el factor VIII de coagulación humano-(1649-2332)-péptido Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 122 Recommended International Non Proprietary Names (Rec. INN): List 59 Dénominations communes internationales proposées (DCI Rec.): Liste 59 Denominaciones Comunes Internacionales Propuestas (DCI Rec.): Lista 59 (WHO Drug Information, Vol. 22, No. 1, 2008) p. 74 & beroctocogum alfa # 75 beroctocog alfa replace the structure by the following one béroctocog alfa remplacer la structure par la suivante beroctocog alfa sustitúyase la estructura por la siguiente CO2H NH2H O S HO O O Heavy chain / Chaîne lourde / Cadena pesada ATRRYYLGAV ELSWDYMQSD LGELPVDARF PPRVPKSFPF NTSVVYKKTL 50 FVEFTDHLFN IAKPRPPWMG LLGPTIQAEV YDTVVITLKN MASHPVSLHA 100 VGVSYWKASE GAEYDDQTSQ REKEDDKVFP GGSHTYVWQV LKENGPMASD 150 PLCLTYSYLS HVDLVKDLNS GLIGALLVCR EGSLAKEKTQ TLHKFILLFA 200 VFDEGKSWHS ETKNSLMQDR DAASARAWPK MHTVNGYVNR SLPGLIGCHR 250 KSVYWHVIGM GTTPEVHSIF LEGHTFLVRN HRQASLEISP ITFLTAQTLL 300 MDLGQFLLFC HISSHQHDGM EAYVKVDSCP EEPQLRMKNN EEAEDYDDDL 350 TDSEMDVVRF DDDNSPSFIQ IRSVAKKHPK TWVHYIAAEE EDWDYAPLVL 400 APDDRSYKSQ YLNNGPQRIG RKYKKVRFMA YTDETFKTRE AIQHESGILG 450 PLLYGEVGDT LLIIFKNQAS RPYNIYPHGI TDVRPLYSRR LPKGVKHLKD 500 FPILPGEIFK YKWTVTVEDG PTKSDPRCLT RYYSSFVNME RDLASGLIGP 550 LLICYKESVD QRGNQIMSDK RNVILFSVFD ENRSWYLTEN IQRFLPNPAG 600 VQLEDPEFQA SNIMHSINGY VFDSLQLSVC LHEVAYWYIL SIGAQTDFLS 650 VFFSGYTFKH KMVYEDTLTL FPFSGETVFM SMENPGLWIL GCHNSDFRNR 700 GMTALLKVSS CDKNTGDYYE DSYEDISAYL LSKNNAIEPR S 741 Light chain / Chaîne légère / Cadena ligera EI 1650 TRTTLQSDQE EIDYDDTISV EMKKEDFDIY DEDENQSPRS FQKKTRHYFI 1700 AAVERLWDYG MSSSPHVLRN RAQSGSVPQF KKVVFQEFTD GSFTQPLYRG 1750 ELNEHLGLLG PYIRAEVEDN IMVTFRNQAS RPYSFYSSLI SYEEDQRQGA 1800 EPRKNFVKPN ETKTYFWKVQ HHMAPTKDEF DCKAWAYFSD VDLEKDVHSG 1850 LIGPLLVCHT NTLNPAHGRQ VTVQEFALFF TIFDETKSWY FTENMERNCR 1900 APCNIQMEDP TFKENYRFHA INGYIMDTLP GLVMAQDQRI RWYLLSMGSN 1950 ENIHSIHFSG HVFTVRKKEE YKMALYNLYP GVFETVEMLP SKAGIWRVEC 2000 LIGEHLHAGM STLFLVYSNK CQTPLGMASG HIRDFQITAS GQYGQWAPKL 2050 ARLHYSGSIN AWSTKEPFSW IKVDLLAPMI IHGIKTQGAR QKFSSLYISQ 2100 FIIMYSLDGK KWQTYRGNST GTLMVFFGNV DSSGIKHNIF NPPIIARYIR 2150 LHPTHYSIRS TLRMELMGCD LNSCSMPLGM ESKAISDAQI TASSYFTNMF 2200 ATWSPSKARL HLQGRSNAWR PQVNNPKEWL QVDFQKTMKV TGVTTQGVKS 2250 LLTSMYVKEF LISSSQDGHQ WTLFFQNGKV KVFQGNQDSF TPVVNSLDPP 2300 LLTRYLRIHP QSWVHQIALR MEVLGCEAQD LY 2332 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 153-179 248-329 528-554 630-711 1832-1858 1899-1903 2021-2169 2174-2326 Modified residues / Résidus modifiés / Restos modificados Y 346-718-719-723-1664-1680 O-sulfoTyr Glycosylation sites (N) / Sites de glycosylation (N) / Posiciones de glicosilación (N) Asn-41 Asn-239 Asn-1810 Asn-2118 delete/supprimer/suprimáse C3821H5813N1003O1139S35 + C3547H5400N956O1033S35 Recommended International Non Proprietary Names (Rec. INN): List 71 Dénominations communes internationales proposées (DCI Rec.): Liste 71 Denominaciones Comunes Internacionales Propuestas (DCI Rec.): Lista 71 (WHO Drug Information, Vol. 28, No. 1, 2014) p. 96 ombitasvirum ombitasvir replace the chemical name by the following one ombitasvir remplacer le nom chimique par le suivant ombitasvir sustitúyase el nombre químico por el siguiente dimethyl N,N'-([(2S,5S)-1-(4-tert-butylphenyl)pyrrolidine- 2,5-diyl]bis{4,1-phenyleneazanediylcarbonyl[(2S)-pyrrolidine- 2,1-diyl][(2S)-3-methyl-1-oxobutane-1,2-diyl]})biscarbamate WHO Drug Information, Vol. 29, No. 1, 2015 Recommended INN: List 73 123 N,N'-([(2S,5S)-1-(4-tert-butylphényl)pyrrolidine-2,5-diyl]bis{4,1- phénylèneazanediylcarbonyl[(2S)-pyrrolidine-2,1-diyl][(2S)-3-méthyl- 1-oxobutane-1,2-diyl]})biscarbamate de diméthyle N,N'-([(2S,5S)-1-(4-terc-butilfenil)pirrolidina-2,5-diil]bis{4,1- fenilenoazanodiilcarbonil[(2S)-pirrolidina-2,1-diil][(2S)-3-metil- 1-oxobutano-1,2-diil]})biscarbamato de dimetilo p. 98 paclitaxelum trevatidum & 99 paclitaxel trevatide replace the chemical name by the following one paclitaxel trévatide remplacer le nom chimique par le suivant paclitaxel trevatida sustitúyase el nombre químico por el siguiente short modified fragment of human amyloid beta A4 protein covalently linked to three molecules of paclitaxel through succinyl linkers: N2.1,N6.10,N6.15-tris(4-{[(1S,2R)-1-benzamido-3-{[4,10β-bis(acetyloxy)- 2α-(benzoyloxy)-5β,20-epoxy-1,7β-dihydroxy-9-oxotax-11-en-13α- yl]oxy}-3-oxo-1-phenylpropan-2-yl]oxy}-4-oxobutanoyl) ([318-L- threonine(P>T1),324-L-serine(C>S7),325-L-arginine(G>R8),327-L- lysine(N>K10),332-L-lysine(D>K15)] human amyloid beta A4 protein precursor-(318-336)-peptide) fragment court et modifié de la protéine bêta A4 amyloïde humaine lié de façon covalente à trois molécules de paclitaxel par autant de succinyles : N2.1,N6.10,N6.15-tris(4-{[(1S,2R)-1-benzamido-3-{[4,10β-bis(acétyloxy)- 2α-(benzoyloxy)-5β,20-époxy-1,7β-dihydroxy-9-oxotax-11-en-13α- yl]oxy}-3-oxo-1-phénylpropan-2-yl]oxy}-4-oxobutanoyl) ([318-L- thréonine(P>T1),324-L-sérine(C>S7),325-L-arginine(G>R8),327-L- lysine(N>K10),332-L-lysine(D>K15)] précurseur de la protéine amyloïde bêta A4 humaine-(318-336)-peptide) fragmento corto y modificado de la proteína beta A4 amiloide humana unido covalentemente a tres moléculas de paclitaxel mediante succinilos : N2.1,N6.10,N6.15-tris(4-{[(1S,2R)-1-benzamido-3-{[4,10β-bis(acetiloxi)- 2α-(benzoiloxi)-5β,20-epoxi-1,7β-dihidroxi-9-oxotax-11-en-13α- il]oxi}-3-oxo-1-fenilpropan-2-il]oxi}-4-oxobutanoil) ([318-L- treonina(P>T1),324-L-serina(C>S7),325-L-arginina(G>R8),327-L- lisina(N>K10),332-L-lisina(D>K15)] precursor de la proteína amiloide beta A4 humana-(318-336)-péptido p. 115 vedroprevirum vedroprevir replace the chemical name by the following one védroprévir remplacer le nom chimique par le suivant vedroprevir sustitúyase el nombre químico por el siguiente (1R,2R)-1-{(2S,4R)-1-{(2S)-2-[({[(1R,3r,5S)-bicyclo[3.1.0]hexan- 3-yl]oxy}carbonyl)amino]-3,3-dimethylbutanoyl}-4-[(8-chloro- 7-[2-(morpholin-4-yl)ethoxy]-2-{2-[(propan-2-yl)amino]-1,3-thiazol- 4-yl}quinolin-4-yl)oxy]pyrrolidine-2-carboxamido}- 2-ethylcyclopropane-1-carboxylic acid Recommended INN: List 73 WHO Drug Information, Vol. 29, No. 1, 2015 124 acide (1R,2R)-1-{(2S,4R)-1-{(2S)-2-[({[(1R,3r,5S)- bicyclo[3.1.0]hexan-3-yl]oxy}carbonyl)amino]- 3,3-diméthylbutanoyl}-4-[(8-chloro-7-[2-(morpholin-4-yl)éthoxy]- 2-{2-[(propan-2-yl)amino]-1,3-thiazol-4-yl}quinoléin- 4-yl)oxy]pyrrolidine-2-carboxamido}-2-éthylcyclopropane- 1-carboxylique ácido (1R,2R)-1-{(2S,4R)-1-{(2S)-2-[({[(1R,3r,5S)- biciclo[3.1.0]hexan-3-il]oxi}carbonil)amino]-3,3-dimetilbutanoil}- 4-[(8-cloro-7-[2-(morfolin-4-il)etoxi]-2-{2-[(propan-2-il)amino]- 1,3-tiazol-4-il}quinolin-4-il)oxi]pirrolidina-2-carboxamido}- 2-etilciclopropano-1-carboxílico # Electronic structure available on Mednet: http://mednet.who.int/ # Structure électronique disponible sur Mednet: http://mednet.who.int/ # Estructura electrónica disponible en Mednet: http://mednet.who.int/   * http://www.who.int/entity/medicines/services/inn/Radical_Book_2012.pdf Procedure and Guiding Principles / Procédure et Directives / Procedimientos y principios generales The text of the Procedures for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances and General Principles for Guidance in Devising International Nonproprietary Names for Pharmaceutical Substances will be reproduced in proposed INN lists only. Les textes de la Procédure à suivre en vue du choix de dénominations communes internationales recommandées pour les substances pharmaceutiques et des Directives générales pour la formation de dénominations communes internationales applicables aux substances pharmaceutiques seront publiés seulement dans les listes des DCI proposées. El texto de los Procedimientos de selección de denominaciones comunes internacionales recomendadas para las sustancias farmacéuticas y de los Principios generales de orientación para formar denominaciones comunes internacionales para sustancias farmacéuticas aparece solamente en las listas de DCI propuestas.