Jiangsu Key Laboratory of New Drug Research & Clinical Pharmacy, Xuzhou Medical University, Yunlong, 221000 Xuzhou, Jiangsu, China.
Future Med Chem. 2020 Mar;12(6):533-561. doi: 10.4155/fmc-2019-0312. Epub 2020 Feb 12.
Acetyl-CoA carboxylase (ACC), a critical enzyme in the regulation of fatty acid synthesis and metabolism, has emerged as an attractive target for a plethora of emerging diseases, such as diabetes mellitus, nonalcoholic fatty liver disease, cancer, bacterial infections and so on. With decades of efforts in medicinal chemistry, significant progress has been made toward the design and discovery of a considerable number of inhibitors of this enzyme. In this review, we not only clarify the role of ACC in emerging diseases, but also summarize recent developments of potent ACC inhibitors and discuss their molecular mechanisms of action and potentials as novel drugs as well as future perspectives toward the design and discovery of novel ACC inhibitors.
乙酰辅酶 A 羧化酶(ACC)是调节脂肪酸合成和代谢的关键酶,它已成为许多新兴疾病(如糖尿病、非酒精性脂肪肝疾病、癌症、细菌感染等)的一个有吸引力的治疗靶点。经过几十年的药物化学研究,人们在设计和发现该酶的抑制剂方面取得了显著进展。在这篇综述中,我们不仅阐明了 ACC 在新兴疾病中的作用,还总结了强效 ACC 抑制剂的最新研究进展,并讨论了它们的作用机制以及作为新型药物的潜力,同时对新型 ACC 抑制剂的设计和发现提出了未来展望。