Hsp90β-Selective Inhibitors: Probing the Solvent-Accessible Frontier.

ABSTRACT: Inhibitors of the 90- kDa heat shock protein (Hsp90) family, especially Hsp90β, have been a sought-after therapeutic strategy for the treatment of cancer, neurological disorders, and other diseases. Furthermore, recent studies suggest that their coadministration with other therapies can enhance efficacy. pan-Inhibition of the cytosolic Hsp90α and Hsp90β isoforms has proven to be problematic, since the on-target toxicities have resulted in the failure of most Hsp90 inhibitors that entered clinical trials. Consequently, such outcomes highlight the demand for isoform-selective inhibitors that overcome these detriments. Previously, we reported that subtle modifications to the solvent-exposed region of Hsp90β-selective inhibitors can significantly impact affinity and selectivity. Consequently,

SUBMITTER: D'Amico T 

PROVIDER: S-EPMC12711159 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature