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The extent of PXR mediated gene transcription is increased by coactivators, such cdk1 inhibitor because the p160/SRC family of coactivators, including steroid co activator 1, and peroxisome proliferator activated receptor ? coactivator 1, and decreased by corepressors, such as nuclear receptor corepressor protein, sterol regulatory element binding protein 1, and silencing mediator of retinoid and thyroid hormone receptors, specifically the SMRT isoform.

The reader is referred to recent critiques about the information with the molecular mechanism of PXR activation plus the interplay among PXR with other nuclear receptors.

Other compounds have also been identi?ed as agonists and antagonists of PXR. These include synthetic drugs of various therapeutic NSCLC classes and diverse chemical structures, naturally occurring compounds, endogenous substances, including bile acids and vitamins, and environmental toxicants. In contrast to the volume of information on PXR activation by single chemical entities, considerably less is known about the effect of complex chemical mixtures, such as herbal medicines, on PXR activity. St. Johns wort was the ?rst herbal medicine shown to activate PXR. Since then, various other herbal medicines have also been identi?ed as activators of PXR. The following is an overview of our current knowledge on the effect of speci?c herbal medicines on PXR activity.

forkohlii cdk1 inhibitor of unde?ned chemical composition has been reported to activate mouse PXR based on the experimental ?nding indicating that the extract increases Cyp3a11 messenger RNA expression in primary hepatocytes isolated from wild type mice, whereas it has little or no effect on Cyp3a11 mRNA expression in hepatocytes isolated from PXR knockout mice. As mentioned previously, Cyp3a11 is a gene subject to regulation by PXR. It is not known which individual chemical constituent is directly responsible for or contributes to the activation of mouse PXR by C. forkohlii extract. However, candidate compounds include forskolin and 1,9 dideoxyforskolin, which is another diterpene present in the roots of C. forkohlii. Each of these chemicals has been shown to act as an agonist of mouse PXR, as judged by their ability to bind to the ligandbinding domain of PXR, recruit coactivator to PXR, and dissociate corepressor from PXR.

It has medicinal value in traditional Ayurvedic medicine. Extracts of guggul, which is the gum resin from the bark of the C. mukul tree, is available as an over thecounter dietary supplement in various Western countries, including the USA.