@inbook{f6732ffe45fc4952bf90d9fee5cac6cb,
title = "Tactics to avoid inhibition of cytochrome P450s",
abstract = "This chapter will focus on avoiding inhibition of cytochrome P450s. This problem leads to drug–drug interactions that can severely restrict the patients who can receive a particular drug. The first sections [(1) background and motivation, (2) the structure of the cytochrome P450s, and (3) overview of the mechanism of cytochrome P450s] provide essential background to understanding both the problem and some of the solutions. The subsequent three sections [(4) trends for inhibition to be modulated by bulk properties (database analysis), (5) metal chelation, and (6) reactive metabolites and mechanism-based inhibition] will outline some general methods for tackling the problem, and each section has a summary in which the strategic approaches that follow from the information are presented. In the final section [(7) examples of successful reduction of P450 liability], how these strategies can be reduced to tactical application is illustrated with published examples.",
keywords = "Cytochrome P450, Inhibition, Lead optimization, Medicinal chemistry",
author = "Leach, {Andrew G.}",
year = "2015",
doi = "10.1007/7355_2013_25",
language = "English",
isbn = "9783642550409",
volume = "9",
series = "Topics in Medicinal Chemistry Series",
publisher = "Springer Nature",
pages = "107--158",
editor = "Meanwell, {Nicholas A.}",
booktitle = "Tactics in contemporary drug design",
address = "United States",
}