Ligand Screening System for the RXRα Heterodimer Using the Fluorescence RXR Agonist CU-6PMN
Ligand Screening System for the RXRα Heterodimer Using the Fluorescence RXR Agonist CU-6PMN
复制标题
使用荧光 RXR 激动剂 CU-6PMN 的 RXRα 异二聚体配体筛选系统
DOI：
10.1021/acsmedchemlett.2c00509
复制
发表时间：
2023
影响因子：
4.2
通讯作者：
Ito Sohei
中科院分区：
文献类型：
--
作者：
Kawasaki Mayu;Motoyama Tomoharu;Yamada Shoya;Watanabe Masaki;Fujihara Michiko;Kambe Akira;Nakano Shogo;Kakuta Hiroki;Ito Sohei
视黄酸X受体（RXR）是一种以配体结合依赖性方式调节靶基因转录的核受体（NR），是一种令人感兴趣的药物靶标。RXR激动剂已被开发为皮肤侵袭性T细胞淋巴瘤（例如，贝沙罗汀（1））并作为潜在的抗炎剂进行研究。已经报道了用于单独结合RXR的筛选系统。然而，尽管RXR作为RXR异二聚体发挥作用，但直到最近才获得关于评估RXR激动剂作为RXR异二聚体的差异结合的系统的信息。在这里，我们表明，由我们的小组设计的荧光RXR激动剂CU-6PMN（3），可以用于评估RXR与PPARγ/RXRα的结合，并且结合数据不同于单独的RXRα。这种筛选方法为RXR异源二聚体的结合测定开辟了新途径。
Retinoid X receptor (RXR), a nuclear receptor (NR) that regulates transcription of target genes in a ligand binding-dependent manner, is of interest as a drug target. RXR agonists have been developed as therapeutic agents for cutaneous invasive T-cell lymphoma (e.g., bexarotene (1)) and investigated as potential anti-inflammatory agents. Screening systems for the binding of RXR alone have been reported. However, although RXRs function as RXR heterodimers, information on systems to evaluate the differential binding of RXR agonists as RXR heterodimers has not been available until recently. Here we show that the fluorescent RXR agonist CU-6PMN (3), designed by our group, can be useful for assessing RXR binding to PPARγ/RXRα, and that the binding data differ from those of RXRα alone. This screening method opens a new avenue for binding assays for RXR heterodimers.