Details of the Drug Combination

General Information of Drug Combination (ID: DC0LAAI)

Drug Combination Name
Metformin Metyrosine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Metformin   DM89QE1 Metyrosine   DMBYCU0
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 12.2
Bliss Independence Score: 12.2
Loewe Additivity Score: 14.79
LHighest Single Agent (HSA) Score: 14.82

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 [6]
Solute carrier family 47 member 1 (SLC47A1) TTMHCGA S47A1_HUMAN Modulator [7]
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 [8]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [9]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [10]
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [11]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [9]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [12]
Thiamine transporter 1 (SLC19A2) DTLA4Q2 S19A2_HUMAN Substrate [13]
Thiamine transporter 2 (SLC19A3) DT39CEA S19A3_HUMAN Substrate [13]
Equilibrative nucleoside transporter 4 (SLC29A4) DT3EAQP S29A4_HUMAN Substrate [14]
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⏷ Show the Full List of 9 DTP(s)
Indication(s) of Metyrosine
Disease Entry ICD 11 Status REF
Pheochromocytoma 5A75 Approved [5]
Metyrosine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine 3-monooxygenase (TH) TTUHP71 TY3H_HUMAN Binder [15]
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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 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: 6956).
6 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.
7 Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm Res. 2006 Aug;23(8):1696-701.
8 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.
9 Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
10 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.
11 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.
12 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.
13 Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). Mol Pharm. 2015 Dec 7;12(12):4301-10.
14 Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66.
15 Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension. 1991 Jul;18(1):1-8.