Design, synthesis and biological evaluation of tetrazole-containing RXRα ligands as anticancer agents.


School of Pharmaceutical Science, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, 361002, China. Electronic address: [Email]


Nuclear receptor RXRα plays an important role in many biological and pathological processes. The nongenomic action of RXRα is implicated in many cancers. K-8008, a non-canonical RXRα ligand derived from sulindac, inhibits the TNFα-activated PI3K/AKT pathway by mediating the interaction between a truncated form of RXRα (tRXRα) and the p85α regulatory subunit of PI3K and exerts potent anticancer activity in animal model. Herein we report our studies of a novel series of K-8008 analogs as potential anticancer agents targeting RXRα. Two compounds 8b and 18a were identified to have slightly stronger binding to RXRα and improved apoptotic activities in breast cancer cells.


Anticancer activity,Bioisostere,PI3K/AKT pathway,RXRα,RXRα modulator,

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