人源孕烷X受体（hPXR）配体识别残基及基于结构的减轻hPXR反式激活风险策略的简要综述
A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk.
作者信息
Liu Tao, Beck James P, Hao Junliang
机构信息
Discovery Chemistry Research & Technologies, Eli Lilly and Company, Lilly Biotechnology Center 10290 Campus Point Drive San Diego CA 92121 USA
出版信息
RSC Med Chem. 2022 Jan 19;13(2):129-137. doi: 10.1039/d1md00348h. eCollection 2022 Feb 23.
Abstract
The human pregnane X receptor (hPXR) regulates the expression of major drug metabolizing enzymes. A wide range of drug candidates bind and activate hPXR, and hence are at risk of increasing drug-drug interactions and reducing clinical efficacy. hPXR structural features that function as hot spots for ligand binding are identified and highlighted in this concise review. Based on literature structure-activity relationship data as case studies, structure-based strategies to mitigate hPXR transactivation are summarized for medicinal chemists.
摘要
人孕烷X受体（hPXR）调节主要药物代谢酶的表达。众多候选药物可与hPXR结合并激活它，因此存在增加药物相互作用和降低临床疗效的风险。在这篇简要综述中，我们鉴定并强调了作为配体结合热点的hPXR结构特征。以文献中的构效关系数据为案例研究，为药物化学家总结了基于结构的减轻hPXR反式激活的策略。
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