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]
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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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

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

Repurposed Drugs (RPD)

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]

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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]

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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]

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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.