Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors

Expert Opin Investig Drugs. 2019 Oct;28(10):917-930. doi: 10.1080/13543784.2019.1657825. Epub 2019 Aug 29.

Abstract

Introduction: Acetyl-CoA Carboxylase (ACC) is an essential rate-limiting enzyme in fatty acid metabolism. For many years, ACC inhibitors have gained great attention for developing therapeutics for various human diseases including microbial infections, metabolic syndrome, obesity, diabetes, and cancer. Areas covered: We present a comprehensive review and update of ACC inhibitors. We look at the current advance of ACC inhibitors in clinical studies and the implications in drug discovery. We searched ScienceDirect ( https://www.sciencedirect.com/ ), ACS ( https://pubs.acs.org/ ), Wiley ( https://onlinelibrary.wiley.com/ ), NCBI ( https://www.ncbi.nlm.nih.gov/ ) and World Health Organization ( https://www.who.int/ ). The keywords used were Acetyl-CoA Carboxylase, lipid, inhibitors and metabolic syndrome. All documents were published before June 2019. Expert opinion: The key regulatory role of ACC in fatty acid synthesis and oxidation pathways makes it an attractive target for various metabolic diseases. In particular, the combination of ACC inhibitors with other drugs is a new strategy for the treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Expanding the clinical indications for ACC inhibitors will be one of the hot directions in the future. It is also worth looking forward to exploring safe and efficient inhibitors that act on the BC domain of ACC.

Keywords: Acetyl-CoA carboxylase; inhibitors; lipid; metabolic syndrome.

Publication types

  • Review

MeSH terms

  • Acetyl-CoA Carboxylase / antagonists & inhibitors*
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Drug Development / methods
  • Drug Discovery / methods
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acids / metabolism
  • Humans
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / physiopathology
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / physiopathology

Substances

  • Enzyme Inhibitors
  • Fatty Acids
  • ACACA protein, human
  • ACACB protein, human
  • Acetyl-CoA Carboxylase