Differential regulation of CYP3A4 promoter activity by a new class of natural product derivatives binding to pregnane X receptor.

ABSTRACT: The pregnane X receptor (PXR) regulates drug metabolism by regulating the expression of drug-metabolizing enzymes such as cytochrome P450 3A4 (CYP3A4), which is involved in the metabolism of >50% of clinically prescribed drugs. The activity of PXR can be controlled by the binding of small molecule agonists or antagonists. Because of its unique ligand binding pocket, PXR binds promiscuously to structurally diverse chemicals. To study the structure-activity relationship, novel modulators for PXR are needed. Here we report the virtual screening of ∼25,000 natural product derivatives from the ZINC database using the Molecular Operating Environment docking software tool against the PXR-rifampicin complex X-ray crystal structure. Our screening resulted in identification of compounds based on the

SUBMITTER: Banerjee M 

PROVIDER: S-EPMC3777815 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature