Discovery and structure-activity relationship study of phthalimide-phenylpyridine conjugate as inhibitor of Wnt pathway. Issue 7 (1st April 2019)

• Record Type: Journal Article
• Authors: Wu, Hongna; Wu, Jun; Zhang, Wenxuan; Li, Zhongwen; Fang, Jinhui; Lian, Xu; Qin, Tong; Hao, Jie; Zhou, Qi; Wu, Song
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 7(2019)
• Page Start: 870
• Page End: 872
• Publication Date: 2019-04-01
• Subjects: Wnt signaling pathway -- Phthalimide-phenylpyridine conjugate -- Structure-activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.02.009
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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.