Small Molecule Mitochondrial Uncouplers and Their Therapeutic Potential

J Med Chem. 2018 Jun 14;61(11):4641-4655. doi: 10.1021/acs.jmedchem.7b01182.

Elizabeth S Childress ¹, Stephanie J Alexopoulos ², Kyle L Hoehn ² ³, Webster L Santos ¹

Affiliations

1 Department of Chemistry and Virginia Tech Center for Drug Discovery , Virginia Tech , Blacksburg , Virginia 24061 , United States.
2 School of Biotechnology and Biomolecular Sciences , University of New South Wales , Kensington , NSW 2033 , Australia.
3 Departments of Pharmacology and Medicine, Cardiovascular Research Center, and Emily Couric Clinical Cancer Center , University of Virginia , Charlottesville , Virginia 22908 , United States.

PMID: 29156129 DOI: 10.1021/acs.jmedchem.7b01182

Abstract

Small molecule mitochondrial uncouplers transport protons from the mitochondrial inner membrane space into the mitochondrial matrix independent of ATP Synthase, uncoupling nutrient metabolism from ATP generation. The therapeutic potential of mitochondrial uncouplers has been investigated for the treatment of metabolic diseases such as obesity and type 2 diabetes (T2D), ischemia-reperfusion injury, and neurodegenerative diseases. This communication will review the small molecule mitochondrial uncouplers reported to date and explore their potential as therapeutics.

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