Human pregnane X receptor: a novel target for anticancer drug development

• Activation of hPXR results increase in level of DMEs and efflux transporters.
• The hPXR has role in drug–drug interaction and resistance of anticancer drugs.
• The hPXR is a promising target for modulation of chemotherapy.
• We report various approaches for the development of PXR modulators.

Multidrug resistance (MDR), a significant barrier to effective pharmacokinetics and pharmacodynamics of anticancer drugs, is mainly due to the induction potential of anticancer drugs for drug metabolizing enzymes (DMEs) and efflux transporters through nuclear receptors. Human Pregnane X Receptor (hPXR) is master transcription factor for cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1). The hPXR is capable of being activated by structurally diverse ligands. Several studies, like in silico modeling, in vitro assays, and in vivo experimentation have been conducted to identify the structural features of ligand for activation of hPXR. This review highlights hPXR as an appealing target for both the development of novel anticancer drugs and the improvement in preclinical and clinical evaluation of anticancer drugs.

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