Carnell Andrew J, Kirk Ralph, Smith Matthew, McKenna Shane, Lian Lu-Yun, Gibson Robert
Department of Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD (UK).
ChemMedChem. 2013 Oct;8(10):1643-7. doi: 10.1002/cmdc.201300179. Epub 2013 Aug 8.
The enzyme α-methylacyl CoA racemase (AMACR) is involved in the metabolism of branched-chain fatty acids and has been identified as a promising therapeutic target for prostate cancer. By using the recently available human AMACR from HEK293 kidney cell cultures, we tested a series of new rationally designed inhibitors to determine the structural requirements in the acyl component. An N-methylthiocarbamate (Ki=98 nM), designed to mimic the proposed enzyme-bound enolate, was found to be the most potent AMACR inhibitor reported to date.
α-甲基酰基辅酶A消旋酶（AMACR）参与支链脂肪酸的代谢，已被确定为前列腺癌一个有前景的治疗靶点。通过使用最近从HEK293肾细胞培养物中获得的人AMACR，我们测试了一系列新的合理设计的抑制剂，以确定酰基成分中的结构要求。一种设计用于模拟推测的酶结合烯醇化物的N-甲基硫代氨基甲酸盐（Ki = 98 nM）被发现是迄今为止报道的最有效的AMACR抑制剂。
