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metformin   Click here for help

GtoPdb Ligand ID: 4779

Synonyms: Glucophage® | LA-6023
Approved drug PDB Ligand Immunopharmacology Ligand
metformin is an approved drug (FDA (1995))
Compound class: Synthetic organic
Comment: Metformin is the only FDA-approved biguanide class drug. It is formulated as metformin hydrochloride for clinical use. Metformin is often given in fixed-dose combinations with other antihyperglycemic agents.

Repurposing: Cancer cells undergo a metabolic switch to aerobic glycolysis, and become reliant on this metabolic pathway for energy (the Warburg effect). Inhibition of the glycolytic pathway is therefore considered as a tractable therapeutic target in oncology. As metformin is an inhibitor of glycolysis it is being examined for anti-cancer effects in a number of malignancies. Similarly, it is being examined for anti-inflammatory potential since activated immune cells also undergo a metabolic switch to aerobic glycolysis. If found to be effective, this could ultimately lead to metformin being repurposed for indications other than type 2 diabetes.
IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: metformin

metformin is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 2
Topological polar surface area 91.49
Molecular weight 129.1
XLogP -0.54
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CN(C(=N)N=C(N)N)C
Isomeric SMILES CN(C(=N)N=C(N)N)C
InChI InChI=1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)
InChI Key XZWYZXLIPXDOLR-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. DeFronzo RA, Barzilai N, Simonson DC. (1991)
Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects.
J Clin Endocrinol Metab, 73 (6): 1294-301. [PMID:1955512]
2. Hundal RS, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V, Inzucchi SE, Schumann WC, Petersen KF, Landau BR et al.. (2000)
Mechanism by which metformin reduces glucose production in type 2 diabetes.
Diabetes, 49 (12): 2063-9. [PMID:11118008]
3. Koepsell H. (2013)
The SLC22 family with transporters of organic cations, anions and zwitterions.
Mol Aspects Med, 34 (2-3): 413-35. [PMID:23506881]
4. LaMoia TE, Shulman GI. (2021)
Cellular and Molecular Mechanisms of Metformin Action.
Endocr Rev, 42 (1): 77-96. [PMID:32897388]
5. Lee CF, Lo YC, Cheng CH, Furtmüller GJ, Oh B, Andrade-Oliveira V, Thomas AG, Bowman CE, Slusher BS, Wolfgang MJ et al.. (2015)
Preventing Allograft Rejection by Targeting Immune Metabolism.
Cell Rep, 13 (4): 760-770. [PMID:26489460]
6. Masuda S, Terada T, Yonezawa A, Tanihara Y, Kishimoto K, Katsura T, Ogawa O, Inui K. (2006)
Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2.
J Am Soc Nephrol, 17 (8): 2127-35. [PMID:16807400]
7. Schuiveling M, Vazirpanah N, Radstake TRDJ, Zimmermann M, Broen JCA. (2018)
Metformin, A New Era for an Old Drug in the Treatment of Immune Mediated Disease?.
Curr Drug Targets, 19 (8): 945-959. [PMID:28606032]
8. Sebo ZL, Chakrabarty RP, Grant RA, D'Alessandro KB, Koss AR, Blum JLE, Davidson SM, Reczek CR, Chandel NS. (2026)
Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.
Nat Metab, [Epub ahead of print]. [PMID:42103929]
9. Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, Castro RA, Ianculescu AG, Yue L, Lo JC, Burchard EG et al.. (2007)
Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action.
J Clin Invest, 117 (5): 1422-31. [PMID:17476361]
10. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K. (2007)
Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters.
Biochem Pharmacol, 74 (2): 359-71. [PMID:17509534]
11. Zhou M, Xia L, Wang J. (2007)
Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine.
Drug Metab Dispos, 35 (10): 1956-62. [PMID:17600084]