Su Ying, Zeng Zhiping, Chen Ziwen, Xu Dan, Zhang Weidong, Zhang Xiao-Kun
Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, United States.
School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Curr Top Med Chem. 2017;17(6):663-675. doi: 10.2174/1568026616666160617092241.
Retinoid X receptors (RXRs) occupy a central position within the nuclear receptor superfamily. They not only function as important transcriptional factors but also exhibit diverse nongenomic biological activities. The pleiotropic actions of RXRs under both physiological and pathophysiological conditions confer RXRs important drug targets for the treatment of cancer, and metabolic and neurodegenerative diseases. RXR modulators have been studied for the purpose of developing both drug molecules and chemical tools for biological investigation of RXR. Development of RXR modulators has focused on small molecules targeting the canonical ligand-binding pocket. However, accumulating results have demonstrated that there are other binding mechanisms by which small molecules interact with RXR to act as RXR modulators. This review discusses the recent development in the design and discovery of RXR modulators with a focus on those targeting novel binding sites on RXR.
维甲酸X受体（RXRs）在核受体超家族中占据核心地位。它们不仅作为重要的转录因子发挥作用，还表现出多种非基因组生物学活性。RXRs在生理和病理生理条件下的多效性作用使其成为治疗癌症、代谢性疾病和神经退行性疾病的重要药物靶点。为了开发用于RXR生物学研究的药物分子和化学工具，人们对RXR调节剂进行了研究。RXR调节剂的开发主要集中在针对经典配体结合口袋的小分子上。然而，越来越多的研究结果表明，小分子与RXR相互作用作为RXR调节剂还存在其他结合机制。本综述讨论了RXR调节剂设计与发现的最新进展，重点关注那些靶向RXR上新结合位点的调节剂。
