ABSTRACT
This chapter focuses on the advances in the discovery and development of chemical inhibitors against two major human carboxylesterase (CES), including the reported CES inhibitors and their inhibition potency, as well as the structural features of CES inhibitors and the structure-activity relationships. Mammalian carboxylesterases are key members of the serine hydrolase superfamily, which are localized within the lumen of the endoplasmic reticulum (ER) in various tissues. The majority of mammalian carboxylesterases are intracellular proteins found predominantly in the microsomal fraction that encompass the ER. Human carboxylesterases have broad substrate spectra, which can hydrolyze a vast number of endo- and xenobiotic substrates with ester, thioester, carbamate, and amide bonds. The key roles of CES in both human health and xenobiotic metabolism arouse great interest in the discovery of CES inhibitors to modulate endogenous metabolism or to improve the outcomes of patients administrated ester drugs.
