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Solid tumour/cancer 2A00-2F9Z Withdrawn from market [2]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
CHEBI:31856
CAS Number
18378-89-7
UNII
NIJ123W41V
DrugBank ID
DB06810
TTD ID
D06EPF
VARIDT ID
DR01174
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
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
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]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Gene/Protein Processing [6]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [7]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [7]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Gene/Protein Processing [6]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Gene/Protein Processing [6]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Gene/Protein Processing [8]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Gene/Protein Processing [9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Gene/Protein Processing [10]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Gene/Protein Processing [8]
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] [11]
Levomilnacipran DMV26S8 Moderate Increased risk of bleeding by the combination of Plicamycin and Levomilnacipran. Chronic pain [MG30] [12]
Regorafenib DMHSY1I Major Increased risk of bleeding by the combination of Plicamycin and Regorafenib. Colorectal cancer [2B91] [13]
Vortioxetine DM6F1PU Moderate Increased risk of bleeding by the combination of Plicamycin and Vortioxetine. Depression [6A70-6A7Z] [12]
Apigenin DMI3491 Minor Increased risk of bleeding by the combination of Plicamycin and Apigenin. Discovery agent [N.A.] [14]
Avapritinib DMK2GZX Major Increased risk of bleeding by the combination of Plicamycin and Avapritinib. Gastrointestinal stromal tumour [2B5B] [13]
Teriflunomide DMQ2FKJ Major Additive myelosuppressive effects by the combination of Plicamycin and Teriflunomide. Hyper-lipoproteinaemia [5C80] [15]
Ibrutinib DMHZCPO Major Increased risk of bleeding by the combination of Plicamycin and Ibrutinib. Mature B-cell lymphoma [2A85] [16]
Ponatinib DMYGJQO Major Increased risk of bleeding by the combination of Plicamycin and Ponatinib. Mature B-cell lymphoma [2A85] [17]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Plicamycin and Tecfidera. Multiple sclerosis [8A40] [18]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Plicamycin and Siponimod. Multiple sclerosis [8A40] [19]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Plicamycin and Fingolimod. Multiple sclerosis [8A40] [20]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Plicamycin and Ozanimod. Multiple sclerosis [8A40] [13]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Plicamycin when combined with Anthrax vaccine. Sepsis [1G40-1G41] [21]
Brilinta DMBR01X Moderate Increased risk of bleeding by the combination of Plicamycin and Brilinta. Thrombosis [DB61-GB90] [13]
Cabozantinib DMIYDT4 Major Increased risk of bleeding by the combination of Plicamycin and Cabozantinib. Thyroid cancer [2D10] [22]
Betrixaban DM2C4RF Major Increased risk of bleeding by the combination of Plicamycin and Betrixaban. Venous thromboembolism [BD72] [23]
⏷ 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 Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression. Toxicol Appl Pharmacol. 2014 Oct 1;280(1):138-48.
7 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.
8 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.
9 Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter. Gene. 2014 Feb 15;536(1):135-44. doi: 10.1016/j.gene.2013.11.053. Epub 2013 Dec 4.
10 CREB/Sp1-mediated MCL1 expression and NFB-mediated ABCB1 expression modulate the cytotoxicity of daunorubicin in chronic myeloid leukemia cells. Toxicol Appl Pharmacol. 2022 Jan 15;435:115847. doi: 10.1016/j.taap.2021.115847. Epub 2021 Dec 25.
11 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]
12 Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
13 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
14 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]
15 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
16 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
17 Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
18 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
19 Cerner Multum, Inc. "Australian Product Information.".
20 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
21 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]
22 Product Information. Cometriq (cabozantinib). Exelixis Inc, S San Francisco, CA.
23 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]