General Information of Drug Combination (ID: DCV0NPE)

Drug Combination Name
Metformin MK-4827
Indication
Disease Entry Status REF
Malignant melanoma Investigative [1]
Component Drugs Metformin   DM89QE1 MK-4827   DMLYGH4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SKMEL30
Zero Interaction Potency (ZIP) Score: 6.27
Bliss Independence Score: 13.35
Loewe Additivity Score: 1.45
LHighest Single Agent (HSA) Score: 8.39

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Metformin
Disease Entry ICD 11 Status REF
Colorectal carcinoma N.A. Approved [2]
Non-insulin dependent diabetes 5A11 Approved [2]
Ovarian serous cystadenocarcinoma N.A. Approved [2]
Prostate carcinoma N.A. Approved [2]
Type-2 diabetes 5A11 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [4]
Metformin Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Acetyl-CoA carboxylase 2 (ACACB) TTY84UG ACACB_HUMAN Activator [7]
Solute carrier family 47 member 1 (SLC47A1) TTMHCGA S47A1_HUMAN Modulator [8]
HUMAN mannose receptor (MRC1) TTKV8W5 MRC1_HUMAN Inhibitor [4]
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Metformin Interacts with 9 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [10]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [11]
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [12]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [10]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [13]
Thiamine transporter 1 (SLC19A2) DTLA4Q2 S19A2_HUMAN Substrate [14]
Thiamine transporter 2 (SLC19A3) DT39CEA S19A3_HUMAN Substrate [14]
Equilibrative nucleoside transporter 4 (SLC29A4) DT3EAQP S29A4_HUMAN Substrate [15]
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⏷ Show the Full List of 9 DTP(s)
Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [5]
Breast cancer 2C60-2C65 Phase 2 [6]
Ewing sarcoma 2B52 Phase 1 [6]
MK-4827 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Modulator [16]
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MK-4827 Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [17]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [18]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [18]
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MK-4827 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [19]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DC3QMWE NCIH1650 Investigative [1]
Adenocarcinoma DCJHU0K NCIH520 Investigative [1]
Adenocarcinoma DCIB4EE COLO320DM Investigative [1]
Adenocarcinoma DC4RJJL HCT116 Investigative [1]
Adenocarcinoma DC5NYRE HT29 Investigative [1]
Amelanotic melanoma DCVX14L A2058 Investigative [1]
Non small cell carcinoma DC0Y88K SKMES1 Investigative [1]
Ovarian serous cystadenocarcinoma DCFXORH SK-OV-3 Investigative [1]
Breast carcinoma DCX0YG6 OCUBM Investigative [20]
Carcinoma DCBNXOO OV90 Investigative [20]
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⏷ Show the Full List of 10 DrugCom(s)

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 Metformin FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. March 2020
5 ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7 AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. Biochem Pharmacol. 2009 Jun 1;77(11):1684-93.
8 Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm Res. 2006 Aug;23(8):1696-701.
9 Role of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin. Am J Obstet Gynecol. 2010 Apr;202(4):383.e1-7.
10 Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
11 Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005.
12 Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009 Oct;50(4):1227-40.
13 Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
14 Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). Mol Pharm. 2015 Dec 7;12(12):4301-10.
15 Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66.
16 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
17 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
18 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
19 Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
20 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.