Wang Junlai, Liu Sen
Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei University of Technology, Wuhan 430068, Hubei, China.
Hubei WEL-SAFE Biotechnology Co., Ltd., Ezhou 436006, Hubei, China.
Sheng Wu Gong Cheng Xue Bao. 2023 Nov 25;39(11):4397-4412. doi: 10.13345/j.cjb.230143.
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.
单酰甘油脂肪酶（MGL）是一种丝氨酸水解酶，在内源性大麻素2-花生四烯酸甘油酯的降解中起主要作用。MGL在某些癌细胞中的作用已得到证实，抑制MGL活性可抑制细胞增殖。这使得MGL成为一种有前景的癌症治疗药物靶点。最近，MGL共价抑制剂的开发进展迅速。这些药物具有很强的共价结合能力、高亲和力、作用时间长、剂量低和耐药风险低等特点，因此受到越来越多的关注。本文介绍了MGL的结构与功能、共价MGL抑制剂的特点、作用机制及研究进展，为新型MGL共价小分子抑制剂的开发提供参考。
