Details of the Drug

General Information of Drug (ID: DMJ8AUE)

• Drug Name: Plitidepsin
• Synonyms: Aplidin (TN)

Indication

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Phase 3	[1]
Angioimmunoblastic T-cell Lymphoma	2A90.9	Phase 2	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 4:
  Molecular Weight (mw); 1110.3
  Topological Polar Surface Area (xlogp); 5.7
  Rotatable Bond Count (rotbonds); 15
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 15
• ADMET Property: Metabolism: The drug is metabolized via the hepatic [3]
• Chemical Identifiers:
  Formula: C57H87N7O15
  IUPAC Name: (2S)-N-[(2R)-1-[[(3S,6S,8S,12S,13R,16S,17R,20S,23S)-13-[(2S)-butan-2-yl]-12-hydroxy-20-[(4-methoxyphenyl)methyl]-6,17,21-trimethyl-3-(2-methylpropyl)-2,5,7,10,15,19,22-heptaoxo-8-propan-2-yl-9,18-dioxa-1,4,14,21-tetrazabicyclo[21.3.0]hexacosan-16-yl]amino]-4-methyl-1-oxopentan-2-yl]-N-methyl-1-(2-oxopropanoyl)pyrrolidine-2-carboxamide
  Canonical SMILES: CC[C@H](C)[C@@H]1[C@H](CC(=O)O[C@H](C(=O)[C@@H](C(=O)N[C@H](C(=O)N2CCC[C@H]2C(=O)N([C@H](C(=O)O[C@@H]([C@@H](C(=O)N1)NC(=O)[C@@H](CC(C)C)N(C)C(=O)[C@@H]3CCCN3C(=O)C(=O)C)C)CC4=CC=C(C=C4)OC)C)CC(C)C)C)C(C)C)O
  InChI: InChI=1S/C57H87N7O15/c1-15-33(8)46-44(66)29-45(67)79-49(32(6)7)48(68)34(9)50(69)58-39(26-30(2)3)54(73)64-25-17-19-41(64)56(75)62(13)43(28-37-20-22-38(77-14)23-21-37)57(76)78-36(11)47(52(71)59-46)60-51(70)42(27-31(4)5)61(12)55(74)40-18-16-24-63(40)53(72)35(10)65/h20-23,30-34,36,39-44,46-47,49,66H,15-19,24-29H2,1-14H3,(H,58,69)(H,59,71)(H,60,70)/t33-,34-,36+,39-,40-,41-,42+,43-,44-,46+,47-,49-/m0/s1
  InChIKey: UUSZLLQJYRSZIS-LXNNNBEUSA-N
• Cross-matching ID:
  PubChem CID: 9812534
  ChEBI ID: CHEBI:90205
  CAS Number: 137219-37-5
  DrugBank ID: DB04977
  TTD ID: D07QJK
  INTEDE ID: DR1309

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Palmitoyl-protein thioesterase 1 (PPT1)	TTSQC14	PPT1_HUMAN	Modulator	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Substrate	[5]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Substrate	[5]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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• [16] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [17] Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
• [18] Psychotropic drug interactions with valproate. Clin Neuropharmacol. 2005 Mar-Apr;28(2):96-101.
• [19] The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
• [20] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [21] CYP2A6- and CYP2A13-catalyzed metabolism of the nicotine delta-5'(1')iminium ion. J Pharmacol Exp Ther. 2012 Nov;343(2):307-15.
• [22] Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G54-63.
• [23] Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int. 2003 May;63(5):1687-96.
• [24] Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 2010 Mar;44(3):340-55.
• [25] A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300.
• [26] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
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