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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Carboxylesterases - Detoxifying Enzymes and Targets for Drug Therapy

Author(s): Philip M. Potter and Randy M. Wadkins

Volume 13 , Issue 9 , 2006

Page: [1045 - 1054] Pages: 10

DOI: 10.2174/092986706776360969

Price: $65

Abstract

Carboxylesterases (CE) are ubiquitous enzymes responsible for the detoxification of xenobiotics. Many therapeutically useful drugs are metabolized by these proteins which impacts upon the efficiency of drug treatment. In some instances, CEs convert inactive prodrugs to active metabolites, a process that is essential for biological activity. Such compounds include the anticancer agents CPT-11 (3) and capecitabine (4), the antibiotics Ceftin (9) and Vantin, as well as the illicit street drug heroin (6). However, more commonly, CEs hydrolyze many esterified drugs to inactive products that are then excreted. Agents such as flestolol (11), meperidine (5), lidocaine (8) and cocaine (7), are all hydrolyzed and inactivated by these enzymes. Therefore the efficacy of esterified drugs will be dependent upon the distribution and catalytic activity of different CEs. In this review, we examine the structural aspects of CEs and their roles in drug detoxification and propose that modulation of CE activity may allow for improvements in, and potentiation of, drug efficacy.

Keywords: Carboxylesterase, drug metabolism, enzyme structure, inhibitor


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