General Information of Drug Combination (ID: DCIAPS8)

Drug Combination Name
Metformin GSK525762
Indication
Disease Entry Status REF
Breast and ovarian cancer syndrome Investigative [1]
Component Drugs Metformin   DM89QE1 GSK525762   DMPAWBN
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: UWB1289+BRCA1
Zero Interaction Potency (ZIP) Score: 1.15
Bliss Independence Score: 5.02
Loewe Additivity Score: 2
LHighest Single Agent (HSA) Score: 3.8

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 GSK525762
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Phase 1 [5]
Solid tumour/cancer 2A00-2F9Z Phase 1 [6]
GSK525762 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bromodomain-containing protein 4 (BRD4) TTRA6BO BRD4_HUMAN Modulator [17]
Bromodomain and extraterminal domain protein (BET) TTE4BSY NOUNIPROTAC Inhibitor [5]
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GSK525762 Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [18]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [19]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Decreases Expression [19]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [19]
Protein-lysine 6-oxidase (LOX) OT1C2HIU LYOX_HUMAN Decreases Expression [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [20]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [20]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Decreases Expression [16]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) OT25JBA3 F263_HUMAN Increases Expression [16]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Decreases Expression [19]
Endothelial PAS domain-containing protein 1 (EPAS1) OTRE3O8U EPAS1_HUMAN Increases Expression [16]
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⏷ Show the Full List of 11 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCSDAEM CAOV3 Investigative [21]
Adenocarcinoma DC4T3HR NCIH23 Investigative [21]
Adenocarcinoma DCBQNDW COLO320DM Investigative [21]
Adenocarcinoma DC19W0D DLD1 Investigative [21]
Adenocarcinoma DCEH086 HT29 Investigative [21]
Amelanotic melanoma DC0QJTE A2058 Investigative [21]
Germ cell tumour DCT69VE PA1 Investigative [21]
Malignant melanoma DCLJ2R2 RPMI7951 Investigative [21]
Malignant melanoma DCKY3DH SKMEL30 Investigative [21]
Malignant melanoma DC7OTOE UACC62 Investigative [21]
Non small cell carcinoma DC7AINK SKMES1 Investigative [21]
Prostate carcinoma DCVIDGB LNCAP Investigative [21]
Breast and ovarian cancer syndrome DCJQN3R UWB1289 Investigative [1]
Carcinoma DCS1LBA OV90 Investigative [1]
Carcinoma DCPCAEQ EFM192B Investigative [1]
Invasive ductal carcinoma DCA19FU T-47D Investigative [1]
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⏷ Show the Full List of 16 DrugCom(s)

References

1 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.
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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 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: 7033).
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 The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer. Oncogene. 2017 Jan 5;36(1):122-132. doi: 10.1038/onc.2016.184. Epub 2016 Jun 13.
17 Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
18 Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
19 An epigenomic approach to therapy for tamoxifen-resistant breast cancer. Cell Res. 2014 Jul;24(7):809-19. doi: 10.1038/cr.2014.71. Epub 2014 May 30.
20 MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
21 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.