单酰基甘油脂肪酶的共价小分子抑制剂的研究进展

Advances in the development of covalent small molecule inhibitors of monoacylglycerol lipase

摘要:

单酰基甘油脂肪酶(monoacylglycerol lipase, MGL)是一种丝氨酸水解酶，在降解内源性大麻素2-花生四烯酸甘油(2-arachidonoylglycerol, 2-AG)中起主要作用。MGL在部分癌症中的作用已经得到证实，抑制MGL的活性显示出对癌细胞增殖的抑制，这也使MGL成为治疗癌症的一种有前途的新药靶点。目前，MGL的共价抑制剂研发进展较快，此类药物的共价结合能力强，具有高亲合力、持续时间长、剂量低和耐药风险低等特点，因而备受科研人员的关注。本文介绍了MGL的结构功能、共价MGL抑制剂的特点、机制及进展，为新型MGL共价小分子抑制剂的开发提供了参考。

Abstract:

Monoacylglycerol lipase (MGL) is a serine hydrolase that plays a major role in the degradation of endogenous cannabinoid 2-arachidonoylglycerol. The role of MGL in some cancer cells has been confirmed, where inhibition of the MGL activity shows inhibition on cell proliferation. This makes MGL a promising drug target for the treatment of cancer. Recently, the development of covalent inhibitors of MGL has developed rapidly. These drugs have strong covalent binding ability, high affinity, long duration, low dose and low risk of drug resistance, so they have received increasing attention. This article introduces the structure and function of MGL, the characteristics, mechanisms and progress of covalent MGL inhibitors, providing reference for the development of novel covalent small molecule inhibitors of MGL.