Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab 160062, India.
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab 160062, India.
Drug Discov Today. 2014 Jan;19(1):63-70. doi: 10.1016/j.drudis.2013.08.009. Epub 2013 Aug 22.
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.
多药耐药性（MDR）是影响抗癌药物药代动力学和药效学的主要障碍，主要归因于抗癌药物通过核受体对药物代谢酶（DMEs）和外排转运蛋白的诱导潜力。人妊娠相关 X 受体（hPXR）是细胞色素 P450 3A4（CYP3A4）和多药耐药蛋白 1（MDR1）的主要转录因子。hPXR 能够被结构多样的配体激活。已经进行了几项研究，如计算机模拟、体外测定和体内实验，以确定激活 hPXR 的配体的结构特征。本综述强调了 hPXR 作为新型抗癌药物开发和改善抗癌药物临床前和临床评估的有吸引力的靶标。
