The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor.

ABSTRACT: The human pregnane X receptor (hPXR) is activated by a large set of endogenous and exogenous compounds and plays a critical role in the control of detoxifying enzymes and transporters regulating liver and gastrointestinal drug metabolism and clearance. hPXR is also involved in both the development of multidrug resistance and enhanced cancer cells aggressiveness. Moreover, its unintentional activation by pharmaceutical drugs can mediate drug-drug interactions and cause severe adverse events. In that context, the potential of the anticancer BRAF inhibitor dabrafenib suspected to activate hPXR and the human constitutive androstane receptor (hCAR) has not been thoroughly investigated yet. Using different reporter cellular assays, we demonstrate that dabrafenib can activate hPXR as efficiently

SUBMITTER: Creusot N 

PROVIDER: S-EPMC7407672 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature