Halpert J R
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Annu Rev Pharmacol Toxicol. 1995;35:29-53. doi: 10.1146/annurev.pa.35.040195.000333.
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.
同工型选择性细胞色素P450抑制剂极大地促进了对实验动物和人类中单个P450酶的催化特异性以及药理和毒理学意义的表征。在阐明P450底物特异性的酶学决定因素方面的最新进展，现在使得探索抑制剂及其靶酶的互补特性如何决定抑制剂的选择性成为可能。对特异性基础的透彻理解应该能够合理设计新一代基于结构的细胞色素P450抑制剂，用作体内P450功能的探针和调节剂。
