Bhattacharjee Pinaki, Rutland Nicholas, Iyer Malliga R
Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Rockville, Maryland 20852, United States.
J Med Chem. 2022 Dec 22;65(24):16062-16098. doi: 10.1021/acs.jmedchem.2c01265. Epub 2022 Dec 6.
Sterol -acyltransferase (SOAT) is a membrane-bound enzyme that aids the esterification of cholesterol and fatty acids to cholesterol esters. SOAT has been studied extensively as a potential drug target, since its inhibition can serve as an alternative to statin therapy. Two SOAT isozymes that have discrete functions in the human body, namely, SOAT1 and SOAT2, have been characterized. Over three decades of research has focused on candidate SOAT1 inhibitors with unsatisfactory results in clinical trials. Recent research has focused on targeting SOAT2 selectively. In this perspective, we summarize the literature covering various SOAT inhibitory agents and discuss the design, structural requirements, and mode of action of SOAT inhibitors.
固醇酰基转移酶（SOAT）是一种膜结合酶，可促进胆固醇和脂肪酸酯化生成胆固醇酯。由于抑制SOAT可作为他汀类药物治疗的替代方案，因此它作为潜在的药物靶点已得到广泛研究。已鉴定出在人体中具有不同功能的两种SOAT同工酶，即SOAT1和SOAT2。三十多年来的研究主要集中在SOAT1候选抑制剂上，但在临床试验中结果并不理想。最近的研究集中在选择性靶向SOAT2。从这个角度出发，我们总结了涵盖各种SOAT抑制剂的文献，并讨论了SOAT抑制剂的设计、结构要求和作用方式。
