Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery

Title:Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery

Volume: 18 Issue: 12

Author(s): Ogheneochukome Lolodi, Yue-Ming Wang, William C. Wright and Taosheng Chen*

Affiliation:

• Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105,United States

Keywords: Cancer, cytochrome P450, CYP3A4, CYP3A5, drug-drug interactions, drug resistance, drug discovery.

Abstract: Background: Cancer cells use several mechanisms to resist the cytotoxic effects of drugs, resulting in tumor progression and invasion. One such mechanism capitalizes on the body's natural defense against xenobiotics by increasing the rate of xenobiotic efflux and metabolic inactivation. Xenobiotic metabolism typically involves conversion of parent molecules to more soluble and easily excreted derivatives in reactions catalyzed by Phase I and Phase II drug metabolizing enzymes.

Methods: We performed a structured search of peer-reviewed literature on P450 (CYP) 3A, with a focus on CYP3A4 and CYP3A5.

Results: Recent reports indicate that components of the xenobiotic response system are upregulated in some diseases, including many cancers. Such components include the pregnane X receptor (PXR), CYP3A4 and CYP3A5 enzymes. The CYP3A enzymes are a subset of the numerous enzymes that are transcriptionally activated following the interaction of PXR and many ligands.

Conclusion: Intense research is ongoing to understand the functional ramifications of aberrant expression of these components in diseased states with the goal of designing novel drugs that can selectively target them.

Cite this article as:

Lolodi Ogheneochukome, Wang Yue-Ming , Wright C. William and Chen Taosheng *, Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery, Current Drug Metabolism 2017; 18 (12) . https://dx.doi.org/10.2174/1389200218666170531112038