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Structural basis of selective cytochrome P450 inhibition.

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1
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.

Abstract

Isoform-selective cytochrome P450 inhibitors have greatly facilitated the characterization of the catalytic specificities and pharmacological and toxicological significance of individual P450 enzymes in experimental animals and humans. Recent advances in elucidating the enzymatic determinants of P450 substrate specificity now make it possible to explore how complementary properties of inhibitors and their target enzymes dictate inhibitor selectivity. A thorough understanding of the basis of specificity should lead to the rational design of a new generation of structure-based cytochrome P450 inhibitors for use as probes and modulators of P450 function in vivo.

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