CYP3A-Mediated Carbon-Carbon Bond Cleavages in Drug Metabolism

Authors

Junhui Zhou
Xuan Qin
Shenzhi Zhou
Kevin R MacKenzie
Feng Li

Language

English

Publication Date

9-5-2024

Journal

Biomolecules

DOI

10.3390/biom14091125

PMID

39334891

PMCID

PMC11430781

PubMedCentral® Posted Date

9-5-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Cytochrome P450 enzymes (P450s) play a critical role in drug metabolism, with the CYP3A subfamily being responsible for the biotransformation of over 50% of marked drugs. While CYP3A enzymes are known for their extensive catalytic versatility, one intriguing and less understood function is the ability to mediate carbon-carbon (C-C) bond cleavage. These uncommon reactions can lead to unusual metabolites and potentially influence drug safety and efficacy. This review focuses on examining examples of C-C bond cleavage catalyzed by CYP3A, exploring the mechanisms, physiological significance, and implications for drug metabolism. Additionally, examples of CYP3A-mediated ring expansion via C-C bond cleavages are included in this review. This work will enhance our understanding of CYP3A-catalyzed C-C bond cleavages and their mechanisms by carefully examining and analyzing these case studies. It may also guide future research in drug metabolism and drug design, improving drug safety and efficacy in clinical practice.

Keywords

Cytochrome P-450 CYP3A, Humans, Carbon, Pharmaceutical Preparations, Animals, CYP3A, carbon–carbon bond cleavage, drug metabolism

Published Open-Access

yes

Recommended Citation

Zhou, Junhui; Qin, Xuan; Zhou, Shenzhi; et al., "CYP3A-Mediated Carbon-Carbon Bond Cleavages in Drug Metabolism" (2024). Faculty and Staff Publications. 5618.
https://digitalcommons.library.tmc.edu/baylor_docs/5618