Cytochrome P450 Enzymes as Drug Targets in Human Disease [Special Section on Cytochrome P450 Enzymes in Toxicology and as Drug Targets-Minireview]

Abstract

Although the mention of cytochrome P450 (P450) inhibition usually brings to mind unwanted variability in pharmacokinetics, in several cases P450s are good targets for inhibition. These P450s are essential, but in certain disease states, it is desirable to reduce the concentrations of their products. Most of the attention to date has been with human P450s 5A1, 11A1, 11B1, 11B2, 17A1, 19A1, and 51A1. In some of those cases, there are multiple drugs in use, e.g., exemestane, letrozole, and anastrozole with P450 19A1, the steroid aromatase target in breast cancer. There are also several targets that are less developed, e.g., P450s 2A6, 8B1, 4A11, 24A1, 26A1, and 26B1.

SIGNIFICANCE STATEMENT The selective inhibition of certain cytochrome P450s that have major physiological functions has been shown to be very efficacious in certain human diseases. In several cases, the search for better drugs continues.

FootnotesReceived August 29, 2023.Accepted October 2, 2023.

This work was supported by National Institutes of Health National Institute of General Medical Sciences [Grant R01 GM118122] (to F.P.G.).

The author has no actual or perceived conflict of interest with the contents of this article.

dx.doi.org/10.1124/dmd.123.001431.

Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics

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