Details of the Drug

General Information of Drug (ID: DM7C8YV)

Drug Name
Plicamycin
Synonyms A-2371; NSC24559; PA-144; MTM A; AC1O3EQZ; CHEMBL413720; SCHEMBL14066059; NSC-24559; AKOS030213136; EC-7071; CCG-208236; NCGC00160390-01; NCI60_004287; AB01273958-01
Indication
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [1]
Testicular cancer 2C80 Approved [1]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [2]
Lung cancer 2C25.0 Investigative [3]
Ovarian cancer 2C73 Investigative [3]
ATC Code
L01DC02: Plicamycin
L01DC: Other cytotoxic antibiotics
L01D: CYTOTOXIC ANTIBIOTICS AND RELATED SUBSTANCES
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 4 Molecular Weight (mw) 1085.1
Logarithm of the Partition Coefficient (xlogp) 0.6
Rotatable Bond Count (rotbonds) 15
Hydrogen Bond Donor Count (hbonddonor) 11
Hydrogen Bond Acceptor Count (hbondacc) 24
Chemical Identifiers
Formula
C52H76O24
IUPAC Name
(2S,3S)-2-[(2S,4R,5R,6R)-4-[(2S,4R,5S,6R)-4-[(2S,4S,5R,6R)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-3-[(1S,3S,4R)-3,4-dihydroxy-1-methoxy-2-oxopentyl]-6-[(2S,4R,5R,6R)-4-[(2S,4R,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-8,9-dihydroxy-7-methyl-3,4-dihydro-2H-anthracen-1-one
Canonical SMILES
C[C@@H]1[C@H]([C@@H](C[C@@H](O1)O[C@@H]2C[C@@H](O[C@@H]([C@H]2O)C)OC3=CC4=CC5=C(C(=O)[C@H]([C@@H](C5)[C@@H](C(=O)[C@H]([C@@H](C)O)O)OC)O[C@H]6C[C@H]([C@@H]([C@H](O6)C)O)O[C@H]7C[C@H]([C@H]([C@H](O7)C)O)O[C@H]8C[C@]([C@@H]([C@H](O8)C)O)(C)O)C(=C4C(=C3C)O)O)O)O
InChI
InChI=1S/C52H76O24/c1-18-29(72-34-14-30(43(58)21(4)68-34)73-33-13-28(54)42(57)20(3)67-33)12-26-10-25-11-27(49(66-9)48(63)41(56)19(2)53)50(47(62)39(25)46(61)38(26)40(18)55)76-36-16-31(44(59)23(6)70-36)74-35-15-32(45(60)22(5)69-35)75-37-17-52(8,65)51(64)24(7)71-37/h10,12,19-24,27-28,30-37,41-45,49-51,53-61,64-65H,11,13-17H2,1-9H3/t19-,20-,21-,22-,23-,24-,27+,28-,30-,31-,32-,33+,34+,35+,36+,37+,41+,42-,43-,44-,45+,49+,50+,51-,52+/m1/s1
InChIKey
CFCUWKMKBJTWLW-BKHRDMLASA-N
Cross-matching ID
PubChem CID
163659
ChEBI ID
CHEMBL257619
CAS Number
18378-89-7
UNII
NIJ123W41V
DrugBank ID
DB06810
TTD ID
D06EPF
VARIDT ID
DR01174
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Gene/Protein Processing [5]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [6]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Gene/Protein Processing [7]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Gene/Protein Processing [7]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Gene/Protein Processing [8]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Gene/Protein Processing [9]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Gene/Protein Processing [10]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Gene/Protein Processing [11]
UL16-binding protein 1 OTUIBJD0 ULBP1_HUMAN Gene/Protein Processing [10]
Vascular endothelial growth factor C OTJ1ZMHK VEGFC_HUMAN Gene/Protein Processing [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Plicamycin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
ABT-492 DMJFD2I Minor Decreased absorption of Plicamycin due to intestinal mucosa variation caused by ABT-492. Bacterial infection [1A00-1C4Z] [12]
Levomilnacipran DMV26S8 Moderate Increased risk of bleeding by the combination of Plicamycin and Levomilnacipran. Chronic pain [MG30] [13]
Regorafenib DMHSY1I Major Increased risk of bleeding by the combination of Plicamycin and Regorafenib. Colorectal cancer [2B91] [14]
Vortioxetine DM6F1PU Moderate Increased risk of bleeding by the combination of Plicamycin and Vortioxetine. Depression [6A70-6A7Z] [13]
Apigenin DMI3491 Minor Increased risk of bleeding by the combination of Plicamycin and Apigenin. Discovery agent [N.A.] [15]
Avapritinib DMK2GZX Major Increased risk of bleeding by the combination of Plicamycin and Avapritinib. Gastrointestinal stromal tumour [2B5B] [14]
Teriflunomide DMQ2FKJ Major Additive myelosuppressive effects by the combination of Plicamycin and Teriflunomide. Hyper-lipoproteinaemia [5C80] [16]
Ibrutinib DMHZCPO Major Increased risk of bleeding by the combination of Plicamycin and Ibrutinib. Mature B-cell lymphoma [2A85] [17]
Ponatinib DMYGJQO Major Increased risk of bleeding by the combination of Plicamycin and Ponatinib. Mature B-cell lymphoma [2A85] [18]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Plicamycin and Tecfidera. Multiple sclerosis [8A40] [19]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Plicamycin and Siponimod. Multiple sclerosis [8A40] [20]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Plicamycin and Fingolimod. Multiple sclerosis [8A40] [21]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Plicamycin and Ozanimod. Multiple sclerosis [8A40] [14]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Plicamycin when combined with Anthrax vaccine. Sepsis [1G40-1G41] [22]
Brilinta DMBR01X Moderate Increased risk of bleeding by the combination of Plicamycin and Brilinta. Thrombosis [DB61-GB90] [14]
Cabozantinib DMIYDT4 Major Increased risk of bleeding by the combination of Plicamycin and Cabozantinib. Thyroid cancer [2D10] [23]
Betrixaban DM2C4RF Major Increased risk of bleeding by the combination of Plicamycin and Betrixaban. Venous thromboembolism [BD72] [24]
⏷ Show the Full List of 17 DDI Information of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8394).
3 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
4 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
5 SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
6 Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem. 2007 Jan 26;282(4):2615-25. doi: 10.1074/jbc.M606203200. Epub 2006 Nov 22.
7 Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression. Chem Biol Interact. 2010 Jan 5;183(1):181-6. doi: 10.1016/j.cbi.2009.09.018.
8 Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
9 Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
10 The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
11 The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
12 Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
13 Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
14 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
15 Heck AM, DeWitt BA, Lukes AL "Potential interactions between alternative therapies and warfarin." Am J Health Syst Pharm 57 (2000): 1221-7 quiz 1228-30. [PMID: 10902065]
16 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
17 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
18 Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
19 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
20 Cerner Multum, Inc. "Australian Product Information.".
21 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
22 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
23 Product Information. Cometriq (cabozantinib). Exelixis Inc, S San Francisco, CA.
24 Bodiford AB, Kessler FO, Fermo JD, Ragucci KR "Elevated international normalized ratio with the consumption of grapefruit and use of warfarin." SAGE Open Med Case Rep 0 (2013): 1-3. [PMID: 27489634]