ArticleEuropean journal of medicinal chemistry2026
Design, synthesis, and biological properties exhibited by 1,2,3-triazole based Grp94-selective inhibitors.
Article in European journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- The evolution of heat shock protein 90 C-terminal inhibitors: From novobiocin to potential clinical candidates.Cell stress & chaperones · 2026Review
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Authors and funding
7 authors.
Funding
Abstract
Grp94, the endoplasmic reticulum-resident paralog of Hsp90, is responsible for the folding and maturation of several client proteins including integrins and mutant myocilin. Inhibition of Grp94 with small molecules has been shown to reduce cell migration of breast cancer cells and promote degradation of mutant myocilin aggregates. Herein, we describe the development of 1,2,3-triazole based Grp94-selective inhibitors derived from a nitrogen scan on BnIm. Structure-activity relationship studies identified lead compound 47, which manifests 76 nM affinity for Grp94 with 121-fold selectivity over Hsp90α. In cellular studies, compound 47 induced the degradation of integrin α2 in MDA-MB-231 cells and reduced intracellular accumulation of mutant myocilin in human trabecular meshwork cells. These findings supported compound 47 as a potent and selective Grp94-selective inhibitor with therapeutic potential.
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