Chapter 6 - Recent Advances in Acetyl-CoA Carboxylase Inhibitors

Abstract

Publisher Summary This chapter discusses the recent advances made in acetyl– CoA carboxylase inhibitors. Significant progress has been made in the development of potent inhibitors of the two acetyl-CoA carboxylases (ACC) isoforms. A number of different chemotypes have been designed, some of which possess selectivity for ACC1 or ACC2. Published mouse knockout (KO) studies from two research groups, using different constructs and different backgrounds, have provided conflicting results. However, limited in vivo efficacy studies suggest that a beneficial effect may be seen in DIO mouse models of diabetes when treated with an ACC1/2 dual inhibitor, and thus ACC inhibition still remains a promising therapeutic approach. It remains to be seen whether ACC1 or ACC2 selective inhibitors will show beneficial in vivo effects and whether inhibition of ACC will be a useful treatment for metabolic disease in humans. This chapter also discusses the available data showing the efficacy of ACC inhibition in long-term studies.