Sulindac-Derived RXR alpha Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site

CORC > 厦门大学 > 药学院－已发表论文

	Sulindac-Derived RXR alpha Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site
	Chen, Liqun ; Wang, Zhi-Gang ; Aleshin, Alexander E. ; Chen, Fan ; Chen, Jiebo ; Jiang, Fuquan ; Alitongbieke, Gulimiran ; Zeng, Zhiping ; Ma, Yue ; Huang, Mingfeng ; Zhou, Hu ; Cadwell, Gregory ; Zheng, Jian-Feng ; Huang, Pei-Qiang ; Liddington, Robert C. ; Zhang, Xiao-kun ; Su, Ying ; Ceng ZP(曾志平) ; Zhou H(周虎) ; Zheng JF(郑剑峰) ; Huang PQ(黄培强) ; Zhang XK(张晓坤)
刊名	http://dx.doi.org/10.1016/j.chembiol.2014.02.017
	2014-05-22
关键词	RETINOID-X-RECEPTOR SMALL-MOLECULE INHIBITORS TUMOR-NECROSIS-FACTOR VITAMIN-D-RECEPTOR ESTROGEN-RECEPTOR COACTIVATOR-BINDING HORMONE-RECEPTOR SUBCELLULAR-LOCALIZATION PROSTATE-CANCER NUCLEAR EXPORT
英文摘要	U.S. Army Medical Research and Material Command [W81XWH-11-1-0677]; National Institutes of Health [CA140980, GM089927, CA179379]; National Natural Science Foundation of China [NSFC-91129302, NSFC-21332007]; Ministry of Education of China [IRT1037]; Science and Technology Bureau of Xiamen [3502Z20133008]; National Basic Research Program (973 Program) of the Ministry of Science and Technology, China [2010CB833200]; Retinoid X receptor-alpha (RXR alpha), an intriguing and unique drug target, can serve as an intracellular target mediating the anticancer effects of certain nonsteroidal anti-inflammatory drugs (NSAIDs), including sulindac. We report the synthesis and characterization of two sulindac analogs, K-8008 and K-8012, which exert improved anticancer activities over sulindac in a RXR alpha-dependent manner. The analogs inhibit the interaction of the N-terminally truncated RXR alpha (tRXR alpha) with the p85 alpha subunit of PI3K, leading to suppression of AKT activation and induction of apoptosis. Crystal structures of the RXR alpha ligand-binding domain (LBD) with K-8008 or K-8012 reveal that both compounds bind to tetrameric RXR alpha LBD at a site different from the classical ligand-binding pocket. Thus, these results identify K-8008 and K-8012 as tRXR alpha modulators and define a binding mechanism for regulating the nongenomic action of tRXR alpha.
语种	英语
出版者	CELL PRESS
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93076]
专题	药学院－已发表论文
推荐引用方式 GB/T 7714	Chen, Liqun,Wang, Zhi-Gang,Aleshin, Alexander E.,et al. Sulindac-Derived RXR alpha Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site[J]. http://dx.doi.org/10.1016/j.chembiol.2014.02.017,2014.
APA	Chen, Liqun.,Wang, Zhi-Gang.,Aleshin, Alexander E..,Chen, Fan.,Chen, Jiebo.,...&张晓坤.(2014).Sulindac-Derived RXR alpha Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site.http://dx.doi.org/10.1016/j.chembiol.2014.02.017.
MLA	Chen, Liqun,et al."Sulindac-Derived RXR alpha Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site".http://dx.doi.org/10.1016/j.chembiol.2014.02.017 (2014).