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Biochem J. 2015 Nov 1;471(3):307-22. doi: 10.1042/BJ20150497.

Repurposing metformin: an old drug with new tricks in its binding pockets.

Author information

1
Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.
2
Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K. f.cabreiro@ucl.ac.uk.

Abstract

Improvements in healthcare and nutrition have generated remarkable increases in life expectancy worldwide. This is one of the greatest achievements of the modern world yet it also presents a grave challenge: as more people survive into later life, more also experience the diseases of old age, including type 2 diabetes (T2D), cardiovascular disease (CVD) and cancer. Developing new ways to improve health in the elderly is therefore a top priority for biomedical research. Although our understanding of the molecular basis of these morbidities has advanced rapidly, effective novel treatments are still lacking. Alternative drug development strategies are now being explored, such as the repurposing of existing drugs used to treat other diseases. This can save a considerable amount of time and money since the pharmacokinetics, pharmacodynamics and safety profiles of these drugs are already established, effectively enabling preclinical studies to be bypassed. Metformin is one such drug currently being investigated for novel applications. The present review provides a thorough and detailed account of our current understanding of the molecular pharmacology and signalling mechanisms underlying biguanide-protein interactions. It also focuses on the key role of the microbiota in regulating age-associated morbidities and a potential role for metformin to modulate its function. Research in this area holds the key to solving many of the mysteries of our current understanding of drug action and concerted effects to provide sustained and long-life health.

KEYWORDS:

aging; biguanides; cancer; cardiovascular disease; metformin; microbiota; phenformin; type 2 diabetes

PMID:
26475449
PMCID:
PMC4613459
DOI:
10.1042/BJ20150497
[Indexed for MEDLINE]
Free PMC Article

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