Modulation of nuclear receptors on drug-metabolizing enzymes and transporters.
- Author:
Zhi-Hao LIU
1
;
Yan LI
Author Information
1. Department of Drug Metabolism and Pharmacokinetics of Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cytochrome P-450 Enzyme System;
metabolism;
Drug Resistance, Multiple;
Drug Resistance, Neoplasm;
Humans;
Membrane Transport Proteins;
metabolism;
Neoplasms;
metabolism;
Peroxisome Proliferator-Activated Receptors;
metabolism;
Receptors, Cytoplasmic and Nuclear;
metabolism;
Receptors, Steroid;
metabolism
- From:
Acta Pharmaceutica Sinica
2012;47(12):1575-1581
- CountryChina
- Language:Chinese
-
Abstract:
PXR, CAR and PPAR, widely distributed in the body, are important members of the nuclear receptors (NRs) family. The activities and gene expressions of drug-metabolizing enzymes (DMEs) and transporters can be regulated by the activation of NRs, which effect the drug disposition. Multidrug resistance (MDR) is the leading cause of failure in cancer therapy. NRs, including PXR, CAR and PPAR, were shown to regulate the expressions of DMEs and transporters involved in the drug metabolism and clearance, suggesting that the modulation of NRs can be considered as a new target to overcome MDR. This review described the research progress of NR family members PXR, CAR, PPAR and their transcriptional activation mechanism, the regulation of DMEs and transporters by NRs, which may provide a valuable reference for clinical medication and overcome of MDR.
