Modifications of human carboxylesterase for improved prodrug activation.

Expert Opinion on Drug Metabolism & Toxicology
Jason M HatfieldPhilip M Potter

Abstract

Carboxylesterases (CEs) are ubiquitous enzymes responsible for the hydrolysis of numerous clinically useful drugs. As ester moieties are frequently included in molecules to improve their water solubility and bioavailability, de facto they become substrates for CEs. In this review, we describe the properties of human CEs with regard to their ability to activate anticancer prodrugs and demonstrate how structure-based design can be used to modulate substrate specificity and to increase efficiency of hydrolysis. A specific example using CPT-11 and a human liver CE is discussed. However, these techniques can be applied to other enzymes and their associated prodrugs. Structure-guided mutagenesis of CEs can be employed to alter substrate specificity and generate novel enzymes that are efficacious at anticancer prodrug activation.

References

Aug 21, 1992·Journal of Medicinal Chemistry·A Cherif, D Farquhar
Jun 1, 1991·Journal of Pharmacobio-dynamics·T TsujiD Tsuru
Feb 1, 1991·Journal of Medicinal Chemistry·D FarquharB S Andersson
Feb 1, 1990·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·P D Senter
Mar 1, 1996·Environmental Health Perspectives·J R CashmanJ Lin
Apr 7, 1997·Biochemical and Biophysical Research Communications·H SchwerG Schmitz
Aug 1, 1997·Biological & Pharmaceutical Bulletin·S TakaiK Hirano
Apr 4, 1998·Journal of Medicinal Chemistry·D FarquharJ A Nelson
May 23, 1998·Annual Review of Pharmacology and Toxicology·T Satoh, M Hosokawa
Aug 15, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·F SalibaE Cvitkovic
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W L FurmanP J Houghton
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·K S AboodyE Y Snyder
Apr 6, 2001·International Journal of Cancer. Journal International Du Cancer·Y TakedaK Kudo
May 4, 2001·Anti-cancer Drugs·A L SeligsonM Sovak
Dec 18, 2001·Advanced Drug Delivery Reviews·P D Senter, C J Springer
Feb 15, 2002·Bioorganic & Medicinal Chemistry Letters·Wolf WrasidloHolger Lode
Feb 28, 2002·Combinatorial Chemistry & High Throughput Screening·Yanbin LiuRichard H Himes
Apr 23, 2002·Nature Structural Biology·Sompop BencharitMatthew R Redinbo
Sep 19, 2002·British Journal of Cancer·D OosterhoffW R Gerritsen
Apr 8, 2003·Nature Structural Biology·Sompop BencharitMatthew R Redinbo
Mar 12, 2004·Critical Reviews in Oncology/hematology·Miklos SimonJohn R Murren
Apr 15, 2004·The Journal of Pharmacology and Experimental Therapeutics·Zejin SunWilliam F Bosron
Sep 24, 2004·Current Medicinal Chemistry·Philippe MeresseEmmanuel Bertounesque
Feb 3, 2005·The Journal of Pharmacology and Experimental Therapeutics·S K QuinneyW F Bosron
Mar 8, 2005·Drug Discovery Today·Matthew R Redinbo, Philip M Potter
Mar 22, 2005·Current Medicinal Chemistry. Anti-cancer Agents·K Jin YoonMary K Danks
May 27, 2005·Cancer Chemotherapy and Pharmacology·Christopher L MortonPhilip M Potter

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Citations

Aug 27, 2014·International Journal of Cancer. Journal International Du Cancer·Pernille R JensenMathilde H Lerche
Nov 26, 2009·Chemistry & Biodiversity·Giulio VistoliBernard Testa
Jan 1, 2010·Journal of Pest Science·Shana V StoddardRandy M Wadkins
Sep 25, 2014·Chemical Communications : Chem Comm·Martin Conda-SheridanSamuel I Stupp
Jul 13, 2021·Drug Delivery and Translational Research·Hiral KapalatiyaSarika Wairkar
Jan 7, 2011·Analytical Chemistry·Joana LamegoAna Luísa Simplício

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