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Strategies for the development of highly selective cytochrome P450 inhibitors: Several CYP targets in current research
Affiliation:1. School of Pharmacy, Kitasato University, Tokyo, Japan;2. Research Laboratories, Toyama Chemical Co., Ltd., Toyama, Japan
Abstract:Cytochromes P450 (CYPs) play an important role in the metabolism of endogenic and xenobiotic substances, especially drugs. In addition, many CYPs may serve as targets for disease treatment. However, due to the presence of a common heme, the hydrophobicity of the CYP binding cavity, and the high homology within the binding pocket, most CYP inhibitors lack selectivity, which often leads to drug-drug interactions. Therefore, it is meaningful to develop highly selective CYP inhibitors. In this review, we summarize some of the strategies that have been used to develop highly selective CYP inhibitors, such as the weakening of the heme-binding group interaction, reduction of molecular lipophilicity and introduction of small structural changes within compounds.
Keywords:Cytochromes P450  Selective CYP inhibitor  Drug-drug interaction  Anti-cancer
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