Small-molecule modulators of PXR and CAR.
Small-molecule modulators of PXR and CAR.
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DOI：
10.1016/j.bbagrm.2016.02.013
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Chen T
中科院分区：
文献类型：
--
作者：
Chai SC;Cherian MT;Wang YM;Chen T
两个核受体，孕激素X受体（PXR）和组成型雄甾受体（CAR），通过调节药物代谢酶和转运体的表达，参与外源解毒系统，以降解和排泄外源化学物质或内源代谢物。这篇综述旨在将PXR和CAR的相关性从它们作为主要异种传感器的既定角色扩展到疾病导向领域，强调它们由小分子调节。这些受体的结构研究提供了急需的洞察其结合混杂的性质和导致配体结合的重要因素。关于物种和异构体选择性激活的报告强调，当从动物数据推断到人类时，需要进一步审查，因为动物模型处于早期药物发现的前沿。
Two nuclear receptors, the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), participate in the xenobiotic detoxification system by regulating the expression of drug-metabolizing enzymes and transporters in order to degrade and excrete foreign chemicals or endogenous metabolites. This review aims to expand the perceived relevance of PXR and CAR beyond their established role as master xenosensors to disease-oriented areas, emphasizing their modulation by small molecules. Structural studies of these receptors have provided much-needed insight into the nature of their binding promiscuity and the important elements that lead to ligand binding. Reports of species- and isoform-selective activation highlight the need for further scrutiny when extrapolating from animal data to humans, as animal models are at the forefront of early drug discovery.