General Information of Drug Combination (ID: DC8K20L)

Drug Combination Name
Plicamycin LY335979
Indication
Disease Entry Status REF
Human papillomavirus-related cervical adenocarcinoma Investigative [1]
Component Drugs Plicamycin   DM7C8YV LY335979   DM2KITF
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KB-ChR-8-5-11
Zero Interaction Potency (ZIP) Score: 43.402
Bliss Independence Score: 39.326
Loewe Additivity Score: 26.116
LHighest Single Agent (HSA) Score: 23.969

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Plicamycin
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [2]
Testicular cancer 2C80 Approved [2]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [3]
Lung cancer 2C25.0 Investigative [4]
Ovarian cancer 2C73 Investigative [4]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [7]
------------------------------------------------------------------------------------
Plicamycin Interacts with 16 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Decreases Expression [8]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [9]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [9]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [9]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [10]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [11]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [6]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [12]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [13]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [14]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [6]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [15]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [12]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [16]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [17]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 DOT(s)
Indication(s) of LY335979
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Discontinued in Phase 3 [5]
LY335979 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Multidrug resistance protein 1 (ABCB1) TT3OT40 MDR1_HUMAN Modulator [18]
Multidrug resistance protein 3 (ABCB4) TTJUXV6 MDR3_HUMAN Modulator [18]
------------------------------------------------------------------------------------
LY335979 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [19]
------------------------------------------------------------------------------------

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 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).
4 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
5 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005159)
6 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.
7 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
8 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.
9 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.
10 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.
11 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.
12 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.
13 Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro. Lung. 2004;182(4):251-64. doi: 10.1007/s00408-004-2507-2.
14 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.
15 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.
16 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.
17 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.
18 A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxoru... Clin Cancer Res. 2004 May 15;10(10):3265-72.
19 Clinical disposition, metabolism and in vitro drug-drug interaction properties of omadacycline. Xenobiotica. 2017 Aug;47(8):682-696. doi: 10.1080/00498254.2016.1213465. Epub 2016 Aug 8.