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硬脂酰辅酶A去饱和酶抑制剂发现与开发的最新进展

Recent progress in the discovery and development of stearoyl CoA desaturase inhibitors.

作者信息

Uto Yoshikazu

机构信息

Venture Science Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

出版信息

Chem Phys Lipids. 2016 May;197:3-12. doi: 10.1016/j.chemphyslip.2015.08.018. Epub 2015 Sep 3.

Abstract

Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids from their saturated fatty acid precursors. SCD1 introduces a cis-double bond at the Δ9 position (between carbons 9 and 10) of stearoyl (C18:0) and palmitoyl-CoA (C16:0). SCD1 has been shown to be a crucial factor in lipid metabolism and body weight control. In addition, SCD1 inhibitors are claimed to be new treatments for various diseases, such as skin disorders, nonalcoholic steatohepatitis (NASH), hepatitis C virus (HCV), Alzheimer's disease, or cancer. This review aims to summarize the examples of the recently reported novel SCD1 inhibitors and to highlight the emerging areas of target indications that may hold promise for the development of SCD1 inhibitors.

摘要

硬脂酰辅酶A去饱和酶1(SCD1)是从饱和脂肪酸前体生物合成单不饱和脂肪酸过程中的一种限速酶。SCD1在硬脂酰(C18:0)和棕榈酰辅酶A(C16:0)的Δ9位置(碳9和碳10之间)引入一个顺式双键。SCD1已被证明是脂质代谢和体重控制中的一个关键因素。此外,SCD1抑制剂据称是治疗各种疾病的新方法,如皮肤病、非酒精性脂肪性肝炎(NASH)、丙型肝炎病毒(HCV)、阿尔茨海默病或癌症。本综述旨在总结最近报道的新型SCD1抑制剂的实例,并突出可能为SCD1抑制剂开发带来希望的新兴目标适应症领域。

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