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]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 1 [3]
Affected Organisms
Humans and other mammals
ATC Code
L01XX57: Plitidepsin
L01XX: Other antineoplastic agents
L01X: OTHER ANTINEOPLASTIC AGENTS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 4 Molecular Weight (mw) 1110.3
Logarithm of the Partition Coefficient (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 []
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
UNII
Y76ID234HW
DrugBank ID
DB04977
TTD ID
D07QJK
INTEDE ID
DR1309
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Elongation factor 1-alpha 1 (EEF1A1) OT00THXS EF1A1_HUMAN Drug Response [6]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Gene/Protein Processing [7]
Ras-related C3 botulinum toxin substrate 1 (RAC1) OTKRO61U RAC1_HUMAN Gene/Protein Processing [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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)
3 ClinicalTrials.gov (NCT04382066) Proof of Concept Study to Evaluate the Safety Profile of Plitidepsin in Patients With COVID-19. U.S. National Institutes of Health.
4 Mode of action and pharmacogenomic biomarkers for exceptional responders to didemnin B
5 In vitro characterization of the human biotransformation pathways of aplidine, a novel marine anti-cancer drug. Invest New Drugs. 2007 Feb;25(1):9-19.
6 Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science. 2021 Feb 26;371(6532):926-931. doi: 10.1126/science.abf4058. Epub 2021 Jan 25.
7 Plitidepsin has a dual effect inhibiting cell cycle and inducing apoptosis via Rac1/c-Jun NH2-terminal kinase activation in human melanoma cells. J Pharmacol Exp Ther. 2008 Mar;324(3):1093-101. doi: 10.1124/jpet.107.132662. Epub 2007 Dec 18.