Development and Characterization of Chemical Tools to Study Ester Drug Metabolic Enzymes in Live Cells [ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)]

Abstract ID 18248

Poster Board 575

Carboxylesterase-mediated metabolism of ester containing drugs can result in their activation or deactivation and enhance clearance. The two major human carboxylesterases (CEss), CES1 and CES2 play a key role in the hydrolysis of xenobiotic esters including aspirin, methylphenidate (Ritalin), oseltamivir (Tamiflu), and the illicit narcotics cocaine and heroin. Despite the established role of CEss in drug metabolism, few techniques exist to study their activity in live cells. Chemical tools have been developed to be able to expand the methods used to study CES activity, however, many existing chemical tools are not sufficiently characterized to be able to confidently study CES activity in live cells. Substrate specificity can overlap with other cellular esterases which makes it exceptionally difficult to differentiate activity between the two carboxylesterases. To address this issue, we report the development of new chemical tools to study CEss. After evaluation for suitability in live cells, we determined their ability to report on CES activity in live cells using small molecule inhibitors and shRNA. Overall, our studies will result in a library of fully characterized chemical tools for studying human carboxylesterases which can lead to improved methods for studying the role of CEss in human health and drug metabolism.

Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics

留言 (0)

沒有登入
gif