Targeting Acetyl-CoA Carboxylases: Small Molecular Inhibitors and their Therapeutic Potential

Authors:
  • DTDi-Jun Tong
    Di-Jun Tong
  • SRSandeep Rajput
    Sandeep Rajput
  • CWChun Wang
    Chun Wang
  • DLDuan-Fang Liao
    Duan-Fang Liao
  • DCDeliang Cao
    Deliang Cao
  • EMEdmund Maser
    Edmund Maser
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Abstract
Acetyl-CoA carboxylases (ACCs) play a rate-limiting role in fatty acid biosynthesis in plants, microbes, mammals and humans. ACCs have the activity of both biotin carboxylase (BC) and carboxyltransferase (CT), catalyzing carboxylation of Acetyl-CoA to malonyl-CoA. In the past years, ACCs have been used as targets for herbicides in agriculture and for drug discovery and development of human diseases, such as microbial infections, diabetes, obesity and cancer. A great number of small molecule ACC inhibitors have been developed, including natural and non-natural (artificial) products. These chemicals target BC reaction, CT reaction or ACC phosphorylation. This article provides a comprehensive review and updates of ACC inhibitors, with a focus on their therapeutic application in metabolic syndromes and malignant diseases. The patent status of common ACC inhibitors is discussed.