Discovery and structure-activity relationship study of phthalimide-phenylpyridine conjugate as inhibitor of Wnt pathway.


State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [Email]


Aberrant Wnt signaling has been implicated in a variety of disease. Inhibition of the Wnt pathway is an attractive approach for developing new therapeutics for the treatment of various types of fibrosis and cancers. We have discovered the phthalimide-phenylpyridine conjugate as a novel hit compound for the Wnt pathway inhibitors from cellular screening. The structure-activity relationship of these compounds suggested both of the substituent group on the phthalimide fragment and the structure of the linker were critical to the inhibitory activity. The most potent compound was about 10-folds more potent than the hit compound, with IC50 value of 0.28 ± 0.01 µM.


Phthalimide-phenylpyridine conjugate,Structure-activity relationship,Wnt signaling pathway,