423:
25:
67:
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1049:
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years of age) on day 1, 8, 15 and 22 of each 28-day cycle until disease progression or unacceptable toxicity. Efficacy was evaluated in a subpopulation of 97 patients who received four or more prior lines of therapy and were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and a CD38-directed antibody. The U.S.
779:(EMA) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Pepaxti, intended for the treatment of multiple myeloma. The applicant for this medicinal product is Oncopeptides AB. Melphalan flufenamide was approved for medical use in the European Union in August 2022.
610:
In the
European Union, melphalan flufenamide is indicated, in combination with dexamethasone, for the treatment of adults with multiple myeloma who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and
705:
In a human Phase 1 trial, no dose-limiting toxicities (DLTs) were observed at lower doses. At doses above 50 mg, reversible neutropenias and thrombocytopenias were observed, and particularly evident in heavily pretreated patients. These side-effects are shared by most chemotherapies, including
735:
Efficacy was evaluated in HORIZON (NCT02963493), a multicenter, single-arm trial. Eligible patients were required to have relapsed refractory multiple myeloma. Patients received melphalan flufenamide 40 mg intravenously on day 1 and dexamethasone 40 mg orally (20 mg for patients ≥75
726:
In a Phase 1/2 trial, in solid tumor patients refractory to standard therapy, response evaluation showed disease stabilization in a majority of patients. In relapsed and refractory multiple-myeloma (RRMM) patients, promising activity was seen in heavily pre-treated RRMM patients where conventional
689:
Pharmacokinetic analysis of plasma samples showed a rapid formation of melphalan; concentrations generally exceeded those of melphalan flufenamide during ongoing infusion. Melphalan flufenamide rapidly disappeared from plasma after infusion, while melphalan typically peaked a few minutes after the
1235:
Gullbo J, Dhar S, Luthman K, Ehrsson H, Lewensohn R, Nygren P, et al. (September 2003). "Antitumor activity of the alkylating oligopeptides J1 (L-melphalanyl-p-L-fluorophenylalanine ethyl ester) and P2 (L-prolyl-m-L-sarcolysyl-p-L-fluorophenylalanine ethyl ester): comparison with melphalan".
635:
belonging to a group of alkylating agents developed more than 50 years ago. Substantial clinical experience has been accumulated about melphalan since then. Numerous derivatives of melphalan, designed to increase the activity or selectivity, have been developed and investigated
813:
Berglund Å, Ullén A, Lisyanskaya A, Orlov S, Hagberg H, Tholander B, et al. (December 2015). "First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies".
697:), degrades proteins and peptides with a N-terminal neutral amino acid. Aminopeptidase N is frequently overexpressed in tumors and has been associated with the growth of different human cancers suggesting it as a suitable target for anti-cancerous therapy.
1694:"Paper: Efficacy of Melflufen, a Peptidase Targeted Therapy, and Dexamethasone in an Ongoing Open-Label Phase 2a Study in Patients with Relapsed and Relapsed-Refractory Multiple Myeloma (RRMM) Including an Initial Report on Progression Free Survival"
1075:
607:, with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD-38 directed monoclonal antibody.
1322:
Gullbo J, Lindhagen E, Bashir-Hassan S, Tullberg M, Ehrsson H, Lewensohn R, et al. (November 2004). "Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo".
1034:
664:
effects in xenografted animals were also observed, and the results confirmed by M Chesi and co-workers – in a unique genetically engineered mouse model of multiple myeloma – are believed to be predictive of clinical efficacy.
1366:
Gullbo J, Wickström M, Tullberg M, Ehrsson H, Lewensohn R, Nygren P, et al. (July 2003). "Activity of hydrolytic enzymes in tumour cells is a determinant for anti-tumour efficacy of the melphalan containing prodrug J1".
1565:
Wickström M, Viktorsson K, Lundholm L, Aesoy R, Nygren H, Sooman L, et al. (May 2010). "The alkylating prodrug J1 can be activated by aminopeptidase N, leading to a possible target directed release of melphalan".
505:
1071:
740:(FDA) approved melphalan flufenamide based on evidence from a clinical trial of 157 adults with multiple myeloma. The trial was conducted at 17 sites in four countries in Spain, France, Italy and the US.
1205:
Wickström M, Lövborg H, Gullbo J (2006). "Future
Prospects for Old Chemotherapeutic Drugs in the Target-Specific Era; Pharmaceutics, Combinations, Co-Drugs and Prodrugs with Melphalan as an Example".
1279:
Wickström M, Johnsen JI, Ponthan F, Segerström L, Sveinbjörnsson B, Lindskog M, et al. (September 2007). "The novel melphalan prodrug J1 inhibits neuroblastoma growth in vitro and in vivo".
1650:
Wickström M, Haglund C, Lindman H, Nygren P, Larsson R, Gullbo J (June 2008). "The novel alkylating prodrug J1: diagnosis directed activity profile ex vivo and combination analyses in vitro".
1022:
690:
end of infusion. This suggests that melphalan flufenamide is rapidly and widely distributed to extravasal tissues, in which melphalan is formed and thereafter redistributed to plasma.
860:
Strese S, Wickström M, Fuchs PF, Fryknäs M, Gerwins P, Dale T, et al. (October 2013). "The novel alkylating prodrug melflufen (J1) inhibits angiogenesis in vitro and in vivo".
167:
1170:
Gullbo J, Tullberg M, Våbenø J, Ehrsson H, Lewensohn R, Nygren P, et al. (2003). "Structure-activity relationship for alkylating dipeptide nitrogen mustard derivatives".
754:
In
October 2021, Oncopeptides AB announced the withdrawal of Pepaxto from the US market after the OCEAN trial's data showed no improvement in terms of overall survival versus
547:
InChI=1S/C24H30Cl2FN3O3/c1-2-33-24(32)22(16-18-3-7-19(27)8-4-18)29-23(31)21(28)15-17-5-9-20(10-6-17)30(13-11-25)14-12-26/h3-10,21-22H,2,11-16,28H2,1H3,(H,29,31)/t21-,22-/m0/s1
1794:"Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study"
1966:
1766:
895:
772:
660:, demonstrated that melphalan flufenamide induced apoptosis in multiple myeloma cell lines, even those resistant to conventional treatment (including melphalan).
105:
2666:
519:
1148:
758:
in the ITT group (19.8 months in the melphalan flufenamide group versus 25.0 months in the pomalidomide group, HR 1.10, 95% CI 0.85–1.44, p = 0,47).
1852:
1938:
for "A Study of
Melphalan Flufenamide (Melflufen) in Combination With Dexamethasone in Relapsed Refractory Multiple Myeloma Patients (HORIZON)" at
640:
or in animal models. Melphalan flufenamide was synthesized, partly due to previous experience of an alkylating peptide cocktail named
Peptichemio
1865:
Text was copied from this source which is copyright
European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
997:
Text was copied from this source which is copyright
European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
3642:
1959:
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1697:
1469:"Melphalan-flufenamide is cytotoxic and potentiates treatment with chemotherapy and the Src inhibitor dasatinib in urothelial carcinoma"
2401:
2357:
2235:
1900:
World Health
Organization (2012). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 67".
2160:
587:
Melphalan flufenamide was approved for medical use in the United States in
February 2021, and in the European Union in August 2022.
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The most common adverse reactions include fatigue, nausea, diarrhea, elevated body temperature and respiratory tract infections.
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Chemically, the drug is best described as the ethyl ester of a dipeptide consisting of melphalan and the amino acid 4-fluoro-
1417:"In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells"
693:
This rapid disappearance from plasma is likely due to hydrolytic enzymes. The Zn(2+) dependent ectopeptidase (also known as
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2839:
2217:
3678:
2949:
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1142:
1112:
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therapies had failed; the median
Progression-Free Survival was 9.4 months and the Duration of Response was 9.6 months.
718:
studies indicate that melphalan flufenamide may be successfully combined with standard chemotherapy or targeted agents.
362:
1734:
1072:"FDA Approves Oncopeptides' Pepaxto (melphalan flufenamide) for Patients with Triple-Class Refractory Multiple Myeloma"
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one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy.
1518:"Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy"
627:
Melphalan flufenamide is a peptidase enhanced cytotoxic (PEnC) with a targeted delivery within tumor cells of
619:
Melphalan flufenamide is metabolized by aminopeptidase hydrolysis and by spontaneous hydrolysis on N-mustard.
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923:"The approval and withdrawal of melphalan flufenamide (melflufen): Implications for the state of the FDA"
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574:
1023:"FDA grants accelerated approval to melphalan flufenamide for relapsed or refractory multiple myeloma"
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2999:
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Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, et al. (February 2022).
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Viktorsson K, Shah CH, Juntti T, HĂĄĂĄg P, Zielinska-Chomej K, Sierakowiak A, et al. (May 2016).
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Chesi M, Matthews GM, Garbitt VM, Palmer SE, Shortt J, Lefebure M, et al. (July 2012).
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Chauhan D, Ray A, Viktorsson K, Spira J, Paba-Prada C, Munshi N, et al. (June 2013).
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Please help update this article to reflect recent events or newly available information.
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1767:"Oncopeptides withdraws Pepaxto in US, scale down organization and focus on R&D"
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896:"FDA issues final decision to withdraw approval of Pepaxto (melphalan flufenamide)"
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activity in several models of human cancer. A preclinical study, performed at
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Compared to melphalan, melphalan flufenamide exhibits significantly higher
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In the United States before market withdrawal, melphalan flufenamide was
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2002:
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787:
Melphalan flufenamide is the international nonproprietary name (INN).
2066:
1462:
1460:
382:
1720:
Advancing Health Through Innovation: New Drug Therapy Approvals 2021
743:
The FDA granted the application for melphalan flufenamide under the
504:
495:
1752:
This article incorporates text from this source, which is in the
1052:
This article incorporates text from this source, which is in the
215:
1948:
1839:
1837:
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132:
1101:
1099:
1097:
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1093:
18:
1603:"Aminopeptidase N (CD13) as a target for cancer chemotherapy"
407:
527:
CCOC(=O)(CC1=CC=C(C=C1)F)NC(=O)(CC2=CC=C(C=C2)N(CCCl)CCCl)N
1601:
Wickström M, Larsson R, Nygren P, Gullbo J (March 2011).
714:
No drug interaction studies have been reported. Several
603:
for the treatment of adults with relapsed or refractory
268:)-2-phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate
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2011:
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1074:(Press release). Oncopeptides AB. 1 March 2021.
310:
855:
853:
808:
806:
804:
802:
800:
285:
972:
970:
968:
966:
773:Committee for Medicinal Products for Human Use
1960:
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1013:
1011:
1009:
1007:
1005:
1003:
8:
1066:
1064:
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141:
57:
3062:
2672:
2432:
2147:
2130:
2008:
1967:
1953:
1945:
421:
350:
65:
1913:
1809:
1626:
1541:
1492:
1440:
946:
370:
3683:
796:
544:
524:
417:
330:
261:
1207:Letters in Drug Design & Discovery
1151:from the original on 13 September 2021
56:
390:
114:
7:
1880:Union Register of medicinal products
1737:from the original on 6 December 2022
179:
2236:ribonucleotide reductase inhibitors
301:
2402:Ribonucleotide reductase inhibitor
2358:Ribonucleotide reductase inhibitor
1337:10.1023/B:DRUG.0000036683.10945.bb
921:Olivier T, Prasad V (April 2022).
14:
2161:Dihydrofolate reductase inhibitor
1855:from the original on 26 June 2022
1700:from the original on 6 March 2016
1078:from the original on 1 March 2021
1037:from the original on 1 March 2021
900:U.S. Food and Drug Administration
3686:
1747:
1619:10.1111/j.1349-7006.2010.01826.x
1250:10.1097/00001813-200309000-00006
1137:"Drug Approval Package: Pepaxto"
1047:
465:
462:
456:
450:
23:
552:Key:YQZNKYXGZSVEHI-VXKWHMMOSA-N
2298:Thymidylate synthase inhibitor
2188:Thymidylate synthase inhibitor
1845:"Pepaxti: Pending EC decision"
1107:"Drug Trial Snapshot: Pepaxto"
706:alkylating agents in general.
471:
444:
100:-phenylalanine ethyl ester, J1
1:
2218:Adenosine deaminase inhibitor
2059:Block microtubule disassembly
1876:"Pepaxti Product information"
1811:10.1016/S2352-3026(21)00381-1
1433:10.1158/1078-0432.CCR-12-3752
1293:10.1158/1535-7163.MCT-07-0156
1281:Molecular Cancer Therapeutics
565:, sold under the brand names
1729:Food and Drug Administration
1534:10.1182/blood-2012-02-412783
1485:10.1016/j.molonc.2015.12.013
1381:10.1080/10611860310001647140
1143:Food and Drug Administration
1113:Food and Drug Administration
1029:Food and Drug Administration
939:10.1016/j.tranon.2022.101374
738:Food and Drug Administration
658:Dana–Farber Cancer Institute
211: Withdrawn from market
16:Alkylating type cancer drug
3760:
1219:10.2174/157018006778631893
1184:10.3727/000000003771013071
631:, a widely used classical
434:Chemical and physical data
3637:
3518:Omacetaxine mepesuccinate
3398:Ciltacabtagene autoleucel
3388:Brexucabtagene autoleucel
1849:European Medicines Agency
1664:10.1007/s10637-007-9092-1
1652:Investigational New Drugs
1580:10.1016/j.bcp.2009.12.022
1369:Journal of Drug Targeting
1325:Investigational New Drugs
983:European Medicines Agency
874:10.1016/j.bcp.2013.07.026
828:10.1007/s10637-015-0299-2
816:Investigational New Drugs
777:European Medicines Agency
535:
515:
252:
64:
32:This article needs to be
3570:Talimogene laherparepvec
3503:Nadofaragene firadenovec
3473:Lisocabtagene maraleucel
2422:Topoisomerase inhibitors
2341:DNA polymerase inhibitor
1568:Biochemical Pharmacology
1421:Clinical Cancer Research
1086:– via PR Newswire.
862:Biochemical Pharmacology
96:-phenylalanine-4-fluoro-
3373:Axicabtagene ciloleucel
1977:chemotherapeutic agents
1798:The Lancet. Haematology
1733:(Report). 13 May 2022.
3555:Sitimagene ceradenovec
3453:Idecabtagene vicleucel
3018:Methyl aminolevulinate
1932:Clinical trial number
927:Translational Oncology
695:alanine aminopeptidase
623:Origin and development
3729:Medical controversies
3029:Porphyrin derivatives
2725:Melphalan flufenamide
2372:Hypomethylating agent
1981:antineoplastic agents
575:anticancer medication
563:Melphalan flufenamide
143:Melphalan flufenamide
59:Melphalan flufenamide
3358:Asparagine depleters
3287:Receptor antagonists
3201:+abiraterone acetate
1902:WHO Drug Information
1033:. 26 February 2021.
722:Therapeutic efficacy
599:in combination with
3408:Denileukin diftitox
3308:Retinoid X receptor
3008:Aminolevulinic acid
2830:Triethylenemelamine
2662:Crosslinking of DNA
2393:Deoxyribonucleotide
2332:+gimeracil/oteracil
762:Society and culture
61:
3664:Never to phase III
2466:Etirinotecan pegol
1940:ClinicalTrials.gov
1473:Molecular Oncology
1117:. 13 December 2022
902:. 23 February 2024
771:In June 2022, the
3714:Cancer treatments
3709:Alkylating agents
3674:
3673:
3633:
3632:
3590:Tigilanol tiglate
3067:Enzyme inhibitors
2990:
2989:
2986:
2985:
2686:Nitrogen mustards
2656:
2655:
2416:
2415:
2118:
2117:
1773:. 22 October 2021
1427:(11): 3019–3031.
1238:Anti-Cancer Drugs
1172:Oncology Research
1147:. 22 March 2021.
710:Drug interactions
676:
560:
559:
506:Interactive image
403:CompTox Dashboard
219:
210:
135:
99:
95:
53:
52:
3751:
3691:
3690:
3689:
3682:
3595:Tisagenlecleucel
3352:Arsenic trioxide
3063:
2996:Photosensitizers
2787:Alkyl sulfonates
2701:Cyclophosphamide
2673:
2612:Anthracenediones
2433:
2407:Hydroxycarbamide
2148:
2131:
2009:
1969:
1962:
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1946:
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1919:
1917:
1897:
1891:
1890:
1888:
1886:
1872:
1866:
1864:
1862:
1860:
1851:. 23 June 2022.
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1705:
1690:
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1647:
1641:
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1598:
1592:
1591:
1574:(9): 1281–1290.
1562:
1556:
1555:
1545:
1513:
1507:
1506:
1496:
1464:
1455:
1454:
1444:
1412:
1401:
1400:
1363:
1357:
1356:
1319:
1313:
1312:
1287:(9): 2409–2417.
1276:
1270:
1269:
1232:
1223:
1222:
1202:
1196:
1195:
1167:
1161:
1160:
1158:
1156:
1133:
1127:
1126:
1124:
1122:
1103:
1088:
1087:
1085:
1083:
1068:
1057:
1051:
1050:
1046:
1044:
1042:
1019:
998:
996:
994:
992:
974:
961:
960:
950:
918:
912:
911:
909:
907:
892:
886:
885:
857:
848:
847:
822:(6): 1232–1241.
810:
685:Pharmacokinetics
674:
633:chemotherapeutic
605:multiple myeloma
579:multiple myeloma
508:
488:
473:
467:
464:
458:
452:
446:
426:
425:
411:
409:
394:
374:
354:
334:
314:
304:
303:
289:
217:
214:
208:
205:
183:
145:
134:
131:
118:
97:
93:
84:Pepaxto, Pepaxti
69:
62:
60:
48:
45:
39:
27:
26:
19:
3759:
3758:
3754:
3753:
3752:
3750:
3749:
3748:
3744:Withdrawn drugs
3699:
3698:
3697:
3687:
3685:
3677:
3675:
3670:
3669:
3654:Clinical trials
3629:
3335:Other/ungrouped
3330:
3281:
3054:
3034:Porfimer sodium
2982:
2944:
2877:
2834:
2664:
2652:
2536:
2506:
2424:
2412:
2387:
2283:
2203:
2139:
2137:antimetabolites
2135:
2134:DNA precursors/
2126:
2124:DNA replication
2114:
2054:
2024:Vinca alkaloids
2000:
1988:
1973:
1929:
1924:
1923:
1899:
1898:
1894:
1884:
1882:
1874:
1873:
1869:
1858:
1856:
1843:
1842:
1835:
1804:(2): e98–e110.
1791:
1790:
1786:
1776:
1774:
1765:
1764:
1760:
1748:
1740:
1738:
1722:
1718:
1717:
1713:
1703:
1701:
1692:
1691:
1687:
1649:
1648:
1644:
1600:
1599:
1595:
1564:
1563:
1559:
1515:
1514:
1510:
1466:
1465:
1458:
1414:
1413:
1404:
1365:
1364:
1360:
1321:
1320:
1316:
1278:
1277:
1273:
1234:
1233:
1226:
1213:(10): 695–703.
1204:
1203:
1199:
1169:
1168:
1164:
1154:
1152:
1135:
1134:
1130:
1120:
1118:
1105:
1104:
1091:
1081:
1079:
1070:
1069:
1060:
1048:
1040:
1038:
1021:
1020:
1001:
990:
988:
976:
975:
964:
920:
919:
915:
905:
903:
894:
893:
889:
859:
858:
851:
812:
811:
798:
793:
785:
769:
764:
745:priority review
733:
724:
712:
703:
701:Adverse effects
687:
671:
646:
625:
617:
593:
556:
553:
548:
543:
542:
531:
528:
523:
522:
511:
486:
476:
470:
461:
455:
449:
429:
405:
397:
377:
357:
337:
317:
300:
292:
272:
269:
260:
259:
229:Pharmacokinetic
223:
187:
155:
148:
49:
43:
40:
37:
28:
24:
17:
12:
11:
5:
3757:
3755:
3747:
3746:
3741:
3736:
3731:
3726:
3721:
3716:
3711:
3701:
3700:
3696:
3695:
3672:
3671:
3668:
3667:
3666:
3665:
3662:
3651:
3645:
3639:
3638:
3635:
3634:
3631:
3630:
3628:
3627:
3622:
3617:
3612:
3607:
3602:
3597:
3592:
3587:
3582:
3577:
3572:
3567:
3562:
3557:
3552:
3547:
3541:
3530:
3525:
3520:
3515:
3510:
3505:
3500:
3495:
3490:
3485:
3480:
3475:
3470:
3465:
3460:
3455:
3450:
3445:
3440:
3435:
3430:
3425:
3420:
3415:
3410:
3405:
3400:
3395:
3390:
3385:
3380:
3375:
3370:
3354:
3349:
3344:
3338:
3336:
3332:
3331:
3329:
3328:
3316:
3304:
3291:
3289:
3283:
3282:
3280:
3279:
3273:
3268:
3263:
3258:
3246:
3240:
3235:
3230:
3225:
3214:
3208:
3203:
3195:
3188:PARP inhibitor
3184:
3172:
3160:
3148:
3147:
3146:
3141:
3136:
3131:
3119:
3113:
3108:
3103:
3098:
3084:
3071:
3069:
3060:
3056:
3055:
3053:
3052:
3046:
3041:
3036:
3025:
3020:
3015:
3010:
3004:
3002:
2992:
2991:
2988:
2987:
2984:
2983:
2981:
2980:
2974:
2969:
2964:
2954:
2952:
2946:
2945:
2943:
2942:
2936:
2931:
2920:
2915:
2910:
2905:
2893:
2887:
2885:
2879:
2878:
2876:
2875:
2870:
2865:
2860:
2855:
2850:
2844:
2842:
2840:Platinum-based
2836:
2835:
2833:
2832:
2827:
2822:
2817:
2805:
2804:
2798:
2782:
2781:
2776:
2771:
2766:
2756:
2751:
2739:
2738:
2733:
2728:
2718:
2713:
2707:
2698:
2693:
2681:
2679:
2670:
2658:
2657:
2654:
2653:
2651:
2650:
2645:
2640:
2635:
2630:
2624:
2619:
2608:
2602:
2597:
2592:
2587:
2582:
2577:
2567:
2562:
2555:Anthracyclines
2550:
2548:
2538:
2537:
2535:
2534:
2528:
2516:
2514:
2508:
2507:
2505:
2504:
2498:
2493:
2488:
2483:
2478:
2473:
2468:
2463:
2458:
2453:
2441:
2439:
2430:
2418:
2417:
2414:
2413:
2411:
2410:
2397:
2395:
2389:
2388:
2386:
2385:
2379:
2367:
2366:
2353:
2352:
2336:
2335:
2325:
2320:
2315:
2310:
2305:
2293:
2291:
2285:
2284:
2282:
2281:
2275:
2273:Mercaptopurine
2264:
2259:
2254:
2248:
2243:
2227:
2226:
2213:
2211:
2205:
2204:
2202:
2201:
2195:
2184:
2178:
2173:
2168:
2156:
2154:
2145:
2128:
2120:
2119:
2116:
2115:
2113:
2112:
2100:
2094:
2089:
2084:
2079:
2074:
2062:
2060:
2056:
2055:
2053:
2052:
2046:
2041:
2036:
2031:
2019:
2017:
2006:
1990:
1989:
1975:Intracellular
1974:
1972:
1971:
1964:
1957:
1949:
1943:
1942:
1928:
1927:External links
1925:
1922:
1921:
1892:
1867:
1833:
1784:
1758:
1711:
1685:
1658:(3): 195–204.
1642:
1613:(3): 501–508.
1607:Cancer Science
1593:
1557:
1528:(2): 376–385.
1508:
1479:(5): 719–734.
1456:
1402:
1375:(6): 355–363.
1358:
1331:(4): 411–420.
1314:
1271:
1244:(8): 617–624.
1224:
1197:
1178:(3): 113–132.
1162:
1128:
1089:
1058:
999:
987:. 21 June 2022
978:"Pepaxti EPAR"
962:
913:
887:
868:(7): 888–895.
849:
795:
794:
792:
789:
784:
781:
775:(CHMP) of the
768:
765:
763:
760:
732:
729:
723:
720:
711:
708:
702:
699:
686:
683:
670:
667:
645:
642:
624:
621:
616:
613:
592:
589:
577:used to treat
558:
557:
555:
554:
551:
549:
546:
538:
537:
536:
533:
532:
530:
529:
526:
518:
517:
516:
513:
512:
510:
509:
501:
499:
491:
490:
484:
478:
477:
474:
468:
459:
453:
447:
442:
436:
435:
431:
430:
428:
427:
419:DTXSID40191461
414:
412:
399:
398:
396:
395:
387:
385:
379:
378:
376:
375:
367:
365:
359:
358:
356:
355:
347:
345:
339:
338:
336:
335:
327:
325:
319:
318:
316:
315:
307:
305:
294:
293:
291:
290:
282:
280:
274:
273:
271:
270:
263:
255:
254:
253:
250:
249:
245:
244:
239:
233:
232:
225:
224:
222:
221:
212:
202:
200:
194:
193:
189:
188:
186:
185:
172:
170:
164:
163:
158:
156:administration
150:
149:
147:
146:
128:
126:
120:
119:
112:
102:
101:
92:Melflufen, 4--
90:
86:
85:
82:
76:
75:
71:
70:
51:
50:
31:
29:
22:
15:
13:
10:
9:
6:
4:
3:
2:
3756:
3745:
3742:
3740:
3737:
3735:
3732:
3730:
3727:
3725:
3722:
3720:
3717:
3715:
3712:
3710:
3707:
3706:
3704:
3694:
3684:
3680:
3663:
3661:
3658:
3657:
3655:
3652:
3649:
3646:
3644:
3641:
3640:
3636:
3626:
3623:
3621:
3618:
3616:
3613:
3611:
3608:
3606:
3603:
3601:
3598:
3596:
3593:
3591:
3588:
3586:
3583:
3581:
3578:
3576:
3573:
3571:
3568:
3566:
3563:
3561:
3558:
3556:
3553:
3551:
3548:
3545:
3542:
3540:
3536:
3535:
3531:
3529:
3528:Tabelecleucel
3526:
3524:
3521:
3519:
3516:
3514:
3511:
3509:
3506:
3504:
3501:
3499:
3496:
3494:
3491:
3489:
3488:Lurbinectedin
3486:
3484:
3481:
3479:
3476:
3474:
3471:
3469:
3466:
3464:
3461:
3459:
3456:
3454:
3451:
3449:
3446:
3444:
3441:
3439:
3436:
3434:
3431:
3429:
3426:
3424:
3421:
3419:
3416:
3414:
3411:
3409:
3406:
3404:
3401:
3399:
3396:
3394:
3391:
3389:
3386:
3384:
3381:
3379:
3376:
3374:
3371:
3368:
3364:
3360:
3359:
3355:
3353:
3350:
3348:
3345:
3343:
3340:
3339:
3337:
3333:
3326:
3322:
3321:
3317:
3314:
3310:
3309:
3305:
3302:
3298:
3297:
3293:
3292:
3290:
3288:
3284:
3277:
3274:
3272:
3269:
3267:
3264:
3262:
3259:
3257:
3253:
3251:
3247:
3244:
3241:
3239:
3236:
3234:
3231:
3229:
3226:
3224:
3220:
3219:
3215:
3212:
3209:
3207:
3204:
3202:
3199:
3196:
3194:
3190:
3189:
3185:
3182:
3178:
3177:
3173:
3170:
3166:
3165:
3161:
3158:
3154:
3153:
3149:
3145:
3142:
3140:
3137:
3135:
3132:
3130:
3127:
3126:
3125:
3124:
3120:
3117:
3114:
3112:
3109:
3107:
3104:
3102:
3099:
3097:
3093:
3092:
3089:
3085:
3082:
3078:
3077:
3073:
3072:
3070:
3068:
3064:
3061:
3057:
3050:
3047:
3045:
3042:
3040:
3037:
3035:
3031:
3030:
3026:
3024:
3021:
3019:
3016:
3014:
3011:
3009:
3006:
3005:
3003:
3001:
2997:
2993:
2978:
2975:
2973:
2970:
2968:
2965:
2963:
2959:
2956:
2955:
2953:
2951:
2950:Intercalation
2947:
2940:
2937:
2935:
2932:
2930:
2926:
2925:
2921:
2919:
2916:
2914:
2911:
2909:
2906:
2903:
2899:
2898:
2894:
2892:
2889:
2888:
2886:
2884:
2880:
2874:
2871:
2869:
2866:
2864:
2861:
2859:
2858:Dicycloplatin
2856:
2854:
2851:
2849:
2846:
2845:
2843:
2841:
2837:
2831:
2828:
2826:
2823:
2821:
2818:
2816:
2813:
2811:
2807:
2806:
2802:
2799:
2797:
2793:
2790:
2788:
2784:
2783:
2780:
2777:
2775:
2772:
2770:
2767:
2764:
2760:
2757:
2755:
2752:
2750:
2747:
2745:
2741:
2740:
2737:
2734:
2732:
2731:Prednimustine
2729:
2726:
2722:
2719:
2717:
2714:
2711:
2708:
2706:
2702:
2699:
2697:
2694:
2692:
2689:
2687:
2683:
2682:
2680:
2678:
2674:
2671:
2668:
2663:
2659:
2649:
2646:
2644:
2641:
2639:
2636:
2634:
2631:
2628:
2625:
2623:
2620:
2618:
2614:
2613:
2609:
2606:
2603:
2601:
2598:
2596:
2593:
2591:
2588:
2586:
2583:
2581:
2578:
2575:
2571:
2568:
2566:
2563:
2561:
2557:
2556:
2552:
2551:
2549:
2547:
2546:Intercalation
2543:
2539:
2532:
2529:
2527:
2523:
2522:
2518:
2517:
2515:
2513:
2509:
2502:
2499:
2497:
2494:
2492:
2489:
2487:
2484:
2482:
2479:
2477:
2474:
2472:
2469:
2467:
2464:
2462:
2459:
2457:
2454:
2452:
2448:
2447:
2443:
2442:
2440:
2438:
2434:
2431:
2428:
2423:
2419:
2408:
2404:
2403:
2399:
2398:
2396:
2394:
2390:
2383:
2380:
2378:
2374:
2373:
2369:
2368:
2364:
2360:
2359:
2355:
2354:
2350:
2349:+daunorubicin
2347:
2343:
2342:
2338:
2337:
2333:
2329:
2326:
2324:
2321:
2319:
2316:
2314:
2313:Doxifluridine
2311:
2309:
2306:
2304:
2300:
2299:
2295:
2294:
2292:
2290:
2286:
2279:
2276:
2274:
2270:
2269:
2265:
2263:
2262:Rabacfosadine
2260:
2258:
2255:
2252:
2249:
2247:
2244:
2242:
2238:
2237:
2233:
2229:
2228:
2224:
2220:
2219:
2215:
2214:
2212:
2210:
2206:
2199:
2196:
2194:
2190:
2189:
2185:
2182:
2179:
2177:
2174:
2172:
2169:
2167:
2163:
2162:
2158:
2157:
2155:
2153:
2149:
2146:
2143:
2138:
2132:
2129:
2125:
2121:
2110:
2106:
2105:
2101:
2098:
2095:
2093:
2090:
2088:
2085:
2083:
2080:
2078:
2075:
2073:
2069:
2068:
2064:
2063:
2061:
2057:
2050:
2047:
2045:
2042:
2040:
2037:
2035:
2032:
2030:
2026:
2025:
2021:
2020:
2018:
2015:
2010:
2007:
2004:
1999:
1995:
1991:
1986:
1982:
1978:
1970:
1965:
1963:
1958:
1956:
1951:
1950:
1947:
1941:
1937:
1936:
1931:
1930:
1926:
1916:
1911:
1907:
1903:
1896:
1893:
1881:
1877:
1871:
1868:
1854:
1850:
1846:
1840:
1838:
1834:
1829:
1825:
1821:
1817:
1812:
1807:
1803:
1799:
1795:
1788:
1785:
1772:
1768:
1762:
1759:
1755:
1754:public domain
1736:
1732:
1730:
1721:
1715:
1712:
1699:
1695:
1689:
1686:
1681:
1677:
1673:
1669:
1665:
1661:
1657:
1653:
1646:
1643:
1638:
1634:
1629:
1624:
1620:
1616:
1612:
1608:
1604:
1597:
1594:
1589:
1585:
1581:
1577:
1573:
1569:
1561:
1558:
1553:
1549:
1544:
1539:
1535:
1531:
1527:
1523:
1519:
1512:
1509:
1504:
1500:
1495:
1490:
1486:
1482:
1478:
1474:
1470:
1463:
1461:
1457:
1452:
1448:
1443:
1438:
1434:
1430:
1426:
1422:
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1054:public domain
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1004:
1000:
986:
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730:
728:
721:
719:
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709:
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698:
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691:
684:
682:
680:
679:phenylalanine
668:
666:
663:
659:
655:
651:
643:
641:
639:
634:
630:
622:
620:
614:
612:
608:
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601:dexamethasone
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393:
392:ChEMBL4303060
389:
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373:
369:
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364:
360:
353:
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87:
83:
81:
77:
74:Clinical data
72:
68:
63:
55:
47:
35:
30:
21:
20:
3734:Orphan drugs
3724:Ethyl esters
3575:Tazemetostat
3539:Alitretinoin
3532:
3443:Estramustine
3423:Elsamitrucin
3413:Eflornithine
3367:Pegaspargase
3363:Asparaginase
3356:
3325:Testolactone
3318:
3306:
3294:
3248:
3233:Panobinostat
3216:
3186:
3174:
3162:
3150:
3121:
3086:
3074:
3027:
3023:Padeliporfin
2962:Dactinomycin
2958:Streptomyces
2939:Temozolomide
2934:Mitozolomide
2922:
2913:Mitobronitol
2902:Procarbazine
2895:
2883:Nonclassical
2808:
2785:
2779:Streptozocin
2744:Nitrosoureas
2742:
2724:
2716:Chlorambucil
2710:Trofosfamide
2696:Chlormethine
2691:Bendamustine
2684:
2622:Mitoxantrone
2617:Losoxantrone
2610:
2570:Daunorubicin
2553:
2519:
2456:Camptothecin
2444:
2400:
2370:
2356:
2339:
2323:Fluorouracil
2303:Capecitabine
2296:
2266:
2230:
2216:
2186:
2181:Pralatrexate
2171:Methotrexate
2159:
2102:
2065:
2022:
1933:
1915:10665/109416
1905:
1901:
1895:
1883:. Retrieved
1879:
1870:
1857:. Retrieved
1848:
1801:
1797:
1787:
1775:. Retrieved
1771:Oncopeptides
1770:
1761:
1739:. Retrieved
1726:
1714:
1702:. Retrieved
1688:
1655:
1651:
1645:
1610:
1606:
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1571:
1567:
1560:
1525:
1521:
1511:
1476:
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1424:
1420:
1372:
1368:
1361:
1328:
1324:
1317:
1284:
1280:
1274:
1241:
1237:
1210:
1206:
1200:
1175:
1171:
1165:
1155:12 September
1153:. Retrieved
1140:
1131:
1119:. Retrieved
1110:
1080:. Retrieved
1039:. Retrieved
1026:
989:. Retrieved
981:
930:
926:
916:
904:. Retrieved
899:
890:
865:
861:
819:
815:
786:
770:
767:Legal status
756:pomalidomide
753:
742:
734:
725:
715:
713:
704:
692:
688:
672:
661:
653:
649:
647:
644:Pharmacology
637:
626:
618:
609:
594:
591:Medical uses
586:
583:
570:
566:
562:
561:
265:
198:Legal status
192:Legal status
124:License data
54:
41:
33:
3650:from market
3620:Vorasidenib
3600:Trabectedin
3585:Tiazofurine
3580:Tebentafusp
3565:Tagraxofusp
3523:Plitidepsin
3493:Mitoguazone
3433:Epacadostat
3403:Demecolcine
3347:Aflibercept
3320:Sex steroid
3193:Fuzuloparib
3134:Carfilzomib
3106:Palbociclib
3096:Abemaciclib
3049:Verteporfin
3013:Efaproxiral
2929:Dacarbazine
2891:Altretamine
2873:Satraplatin
2868:Oxaliplatin
2848:Carboplatin
2825:Triaziquone
2796:Mannosulfan
2774:Ranimustine
2754:Fotemustine
2595:Pirarubicin
2580:Doxorubicin
2574:+cytarabine
2560:Aclarubicin
2521:Podophyllum
2446:Camptotheca
2377:Azacitidine
2363:Gemcitabine
2318:Floxuridine
2251:Fludarabine
2246:Clofarabine
2232:Halogenated
2223:Pentostatin
2198:Raltitrexed
2166:Aminopterin
2109:Ixabepilone
2104:Epothilones
2072:Cabazitaxel
2049:Vinorelbine
2034:Vincristine
2029:Vinblastine
2014:microtubule
1935:NCT02963493
1121:14 December
991:14 December
749:orphan drug
489: g·mol
287:380449-51-4
248:Identifiers
161:Intravenous
89:Other names
80:Trade names
3719:Dipeptides
3703:Categories
3615:Verdinexor
3610:Venetoclax
3513:Oblimersen
3508:Navitoclax
3483:Lucanthone
3478:Lonidamine
3468:Lifileucel
3463:Ivosidenib
3458:Imetelstat
3428:Enasidenib
3418:Elesclomol
3383:Bexarotene
3378:Belzutifan
3313:Bexarotene
3301:Atrasentan
3276:Umbralisib
3271:Idelalisib
3261:Copanlisib
3243:Vorinostat
3238:Romidepsin
3228:Entinostat
3223:Belinostat
3181:Masoprocol
3169:Tiazofurin
3157:Anagrelide
3129:Bortezomib
3116:Seliciclib
3111:Ribociclib
3091:inhibitors
3081:Tipifarnib
3044:Temoporfin
3039:Talaporfin
2977:Plicamycin
2972:Mitomycins
2918:Pipobroman
2897:Hydrazines
2863:Nedaplatin
2815:Carboquone
2810:Aziridines
2801:Treosulfan
2749:Carmustine
2736:Uramustine
2705:Ifosfamide
2677:Alkylating
2638:Bisantrene
2627:Pixantrone
2600:Valrubicin
2590:Idarubicin
2585:Epirubicin
2531:Teniposide
2486:Lurtotecan
2481:Irinotecan
2382:Decitabine
2346:Cytarabine
2289:Pyrimidine
2278:Tioguanine
2268:Thiopurine
2257:Nelarabine
2241:Cladribine
2193:Pemetrexed
2176:Pemetrexed
2152:Folic acid
2092:Paclitaxel
2044:Vinflunine
1741:22 January
933:: 101374.
791:References
751:programs.
615:Metabolism
494:3D model (
482:Molar mass
372:F70C5K4786
343:ChemSpider
278:CAS Number
257:IUPAC name
242:hydrolysis
237:Metabolism
44:March 2024
3660:Phase III
3648:Withdrawn
3625:Vosaroxin
3605:Veliparib
3560:Sotorasib
3550:Selinexor
3544:Tretinoin
3534:Retinoids
3448:Glasdegib
3393:Celecoxib
3342:Adagrasib
3266:Duvelisib
3256:Alpelisib
3211:Rucaparib
3198:Niraparib
3139:Oprozomib
3101:Alvocidib
2967:Bleomycin
2924:Triazenes
2908:Etoglucid
2853:Cisplatin
2769:Nimustine
2763:Semustine
2759:Lomustine
2721:Melphalan
2648:Menogaril
2643:Crisnatol
2633:Amsacrine
2605:Zorubicin
2565:Amrubicin
2526:Etoposide
2501:Topotecan
2496:Silatecan
2491:Rubitecan
2476:Gimatecan
2461:Cositecan
2451:Belotecan
2127:inhibitor
2097:Tesetaxel
2087:Ortataxel
2082:Larotaxel
2077:Docetaxel
2039:Vindesine
1908:(1): 72.
1828:245950577
669:Structure
629:melphalan
597:indicated
154:Routes of
116:Monograph
110:Drugs.com
3739:Prodrugs
3693:Medicine
3498:Mitotane
3438:Eribulin
3206:Olaparib
3144:Ixazomib
2820:Thiotepa
2792:Busulfan
2471:Exatecan
2308:Carmofur
2016:assembly
1979: /
1853:Archived
1820:35032434
1735:Archived
1698:Archived
1680:19915448
1672:17922077
1637:21205077
1588:20067771
1552:22451422
1503:26827254
1451:23584492
1397:25203458
1389:14668056
1353:31613292
1345:15292711
1309:22694740
1301:17876040
1266:10282399
1258:14501383
1192:14760861
1149:Archived
1076:Archived
1035:Archived
957:35196605
906:12 March
882:23933387
836:26553306
716:in vitro
650:in vitro
638:in vitro
573:, is an
323:DrugBank
264:Ethyl (2
168:ATC code
138:DailyMed
2427:S phase
2328:Tegafur
2142:S phase
2067:Taxanes
2003:M phase
1885:3 March
1859:26 June
1777:19 June
1704:3 March
1628:7188354
1543:3398763
1494:5423156
1442:4098702
1082:1 March
1041:1 March
948:8866737
844:8207569
731:History
662:In vivo
654:in vivo
571:Pepaxti
567:Pepaxto
440:Formula
352:8111267
332:DB16627
312:9935639
298:PubChem
184:)
178: (
176:L01AA10
140::
34:updated
3679:Portal
3643:WHO-EM
3252:(Pi3K)
2209:Purine
2012:Block
1826:
1818:
1678:
1670:
1635:
1625:
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1299:
1264:
1256:
1190:
955:
945:
880:
842:
834:
520:SMILES
487:498.42
383:ChEMBL
136:
3164:IMPDI
3059:Other
1824:S2CID
1731:(FDA)
1727:U.S.
1723:(PDF)
1676:S2CID
1522:Blood
1393:S2CID
1349:S2CID
1305:S2CID
1262:S2CID
1145:(FDA)
1141:U.S.
1115:(FDA)
1111:U.S.
1031:(FDA)
1027:U.S.
985:(EMA)
840:S2CID
783:Names
540:InChI
496:JSmol
3250:PIKI
3218:HDAC
2667:CCNS
1887:2023
1861:2022
1816:PMID
1779:2023
1743:2023
1706:2016
1668:PMID
1633:PMID
1584:PMID
1548:PMID
1499:PMID
1447:PMID
1385:PMID
1341:PMID
1297:PMID
1254:PMID
1188:PMID
1157:2021
1123:2022
1084:2021
1043:2021
993:2022
953:PMID
908:2024
878:PMID
832:PMID
747:and
652:and
569:and
363:UNII
231:data
106:AHFS
3296:ERA
3152:PhI
3123:PrI
3088:CDK
3000:PDT
1998:MIs
1994:SPs
1985:L01
1910:hdl
1806:doi
1660:doi
1623:PMC
1615:doi
1611:102
1576:doi
1538:PMC
1530:doi
1526:120
1489:PMC
1481:doi
1437:PMC
1429:doi
1377:doi
1333:doi
1289:doi
1246:doi
1215:doi
1180:doi
943:PMC
935:doi
870:doi
824:doi
408:EPA
302:CID
181:WHO
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