Carboxylesterase inhibitors: an update.

Carboxylesterase inhibitors: an update. Curr Med Chem. 2017 Dec 04;: Authors: Zou LW, Jin Q, Wang DD, Qian QK, Hao DC, Ge GB, Yang L Abstract Mammalian carboxylesterases are key serine hydrolases that catalyze the hydrolysis of a wide variety of ester compounds into the corresponding carboxylic acids and alcohols. In human, two major carboxylesterases, CES1 and CES2, have been identified and well-studied over the past decade. CES1 inhibitors have potential applications in the treatment of hypertriglyceridaemia, obesity and type 2 diabetes, owing to that this enzyme plays prominent role in the metabolism of cholesteryl esters. CES2 plays crucial roles in the metabolic activation of many prodrugs including anticancer agents capecitabine and CPT-11. Co-administration with CES2 inhibitors may ameliorate CPT-11 associated life-threatening diarrhea or improve the half-lives of CES2-substrate drugs. The important roles of carboxylesterases in both endogenous and xenobiotic metabolism arouse great interest in the discovery and development of potent and selective inhibitors against these enzymes. This review focused on the application potentials and recent advances in the discovery and development of carboxylesterases inhibitors. The inhibitory capacities and inhibition mechanism of a variety of carboxylesterases inhibitors including synthetic, semi-synthetic and natural compounds have been comprehensive summarized. Furthermore, the key struc...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research