title: Synthesis and SAR study of modulators inhibiting tRXRα-dependent AKT activation.
abstract: RXRα represents an intriguing and unique target for pharmacologic interventions. We recently showed that Sulindac and a designed analog could bind to RXRα and modulate its biological activity, including inhibition of the interaction of an N-terminally truncated RXRα (tRXRα) with the p85α regulatory subunit of phosphatidylinositol-3-OH kinase (PI3K). Here we report the synthesis, testing and SAR of a series of novel analogs of Sulindac as potential modulators for inhibiting tRXRα-dependent AKT activation. A new compound 30 was identified to have improved biological activity.
authors: Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, China.
authors: Zhi-Gang
authors: ZG
authors: Wang
authors: Liqun
authors: L
authors: Chen
authors: Jiebo
authors: J
authors: Chen
authors: Jian-Feng
authors: JF
authors: Zheng
authors: Weiwei
authors: W
authors: Gao
authors: Zhiping
authors: Z
authors: Zeng
authors: Hu
authors: H
authors: Zhou
authors: Xiao-Kun
authors: XK
authors: Zhang
authors: Pei-Qiang
authors: PQ
authors: Huang
authors: Ying
authors: Y
authors: Su
mesh_terms: D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047490:Retinoid X Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013467:Sulindac / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D047490:Retinoid X Receptor alpha; D013467:Sulindac