2234897-35-7Relevant academic research and scientific papers
Discovery of a Potent Grp94 Selective Inhibitor with Anti-Inflammatory Efficacy in a Mouse Model of Ulcerative Colitis
Jiang, Fen,Guo, An-Ping,Xu, Jia-Chen,You, Qi-Dong,Xu, Xiao-Li
, p. 9513 - 9533 (2018)
As the endoplasmic reticulum paralogue of Hsp90, Grp94 chaperones a small set of client proteins associated with some diseases, including cancer, primary open-angle glaucoma, and inflammatory disorders. Grp94-selective inhibition has been a potential therapeutic strategy for these diseases. In this study, inspired by the conclusion that ligand-induced Phe199 shift effect is the structural basis of Grp94-selective inhibition, a series of novel Grp94 selective inhibitors incorporating benzamide moiety were developed, among which compound 54 manifested the most potent Grp94 inhibitory activity with an IC50 value of 2 nM and over 1000-fold selectivity to Grp94 against Hsp90α. In a DSS-induced mouse model of ulcerative colitis (UC), compound 54 exhibited significant anti-inflammatory efficacy. This work provides a potent Grp94 selective inhibitor as probe compound for the biological study of Grp94 and represents the first study that confirms the potential therapeutic efficacy of Grp94-selective inhibitors against UC.
Grp94 inhibitor with benzamide mother nucleus structure and application of inhibitor
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Paragraph 0163; 0165; 0169; 0170, (2018/07/15)
The invention relates to the field of medicinal chemistry, in particular to a benzamide compound (I) with Grp94 inhibitory activity and a preparation method of the benzamide compound. Pharmacodynamicexperiments prove that the compound has the function of treating Grp94-mediated diseases.
