Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Selective inhibition of glucose regulated protein 94 (Grp94), the most structurally unique isoform of heat shock protein 90 (Hsp90), has been implicated in the treatment of various disease states, including primary open-angle glaucoma and metastatic cancer. In this study, nine analogues were designed and synthesized by conformationally restricting KUNG65, a second generation Grp94-selective inhibitor. Conformational constraints were applied to restrict the rotatable bonds and to bias the benzyl moiety into the Grp94 site 1 pocket as well as to reduce the entropic penalty paid upon binding. A fluorescence polarization assay demonstrated that lead compound C6 exhibited an affinity of 5.52 μM for Grp94 and showed no affinity for Hsp90α, indicating its potential as a Grp94-selective inhibitor.
Source: ACS Omega
Authors: Hao Xu, Kyler Pugh, Brian S. J. Blagg
Institution: University of Notre Dame
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,935
OpenAlex ID: W4405987482