Details of the Drug Combination

General Information of Drug Combination (ID: DCL18FJ)

Drug Combination Name
Metformin L-leucine
Indication
Disease Entry Status REF
Type-2 diabetes Phase 1 [1]
Component Drugs Metformin   DM89QE1 L-leucine   DMQHN7I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable

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]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 DTP(s)
Indication(s) of L-leucine
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [5]
L-leucine Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
L-type amino acid transporter 3 (SLC43A1) DTBMSWG LAT3_HUMAN Substrate [15]
L-type amino acid transporter 4 (SLC43A2) DTK02I1 LAT4_HUMAN Substrate [16]
L-type amino acid transporter 1 (SLC7A5) DT48T0N LAT1_HUMAN Substrate [17]
------------------------------------------------------------------------------------
L-leucine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Leucyl-tRNA synthetase (LARS2) DEP7BTH SYLM_HUMAN Metabolism [18]
------------------------------------------------------------------------------------
L-leucine Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Large neutral amino acids transporter small subunit 2 (SLC7A8) OT8XXVO8 LAT2_HUMAN Affects Import [19]
Amino acid transporter heavy chain SLC3A2 (SLC3A2) OTBR33M9 4F2_HUMAN Affects Import [19]
ATP-binding cassette sub-family C member 8 (ABCC8) OTCWQ54I ABCC8_HUMAN Increases ADR
------------------------------------------------------------------------------------

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 3312).
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 Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters. J Biol Chem. 2003 Oct 31;278(44):43838-45.
16 Anticipation of food intake induces phosphorylation switch to regulate basolateral amino acid transporter LAT4 (SLC43A2) function. J Physiol. 2019 Jan;597(2):521-542.
17 Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009 Feb 6;136(3):521-34.
18 Expression and characterization of the human mitochondrial leucyl-tRNA synthetase. Biochim Biophys Acta. 2000 Feb 29;1490(3):245-58.
19 Methylmercury Uptake into BeWo Cells Depends on LAT2-4F2hc, a System L Amino Acid Transporter. Int J Mol Sci. 2017 Aug 8;18(8):1730. doi: 10.3390/ijms18081730.