The Hsp90β Isoform: An Attractive Target for Drug Development

Med Res Rev. 2025 Sep;45(5):1452-1465. doi: 10.1002/med.22114.

Subhabrata Chaudhury ¹, Terin D'Amico ², Brian S J Blagg ¹

Affiliations

1 Department of Chemistry and Biochemistry, Warren Family Research Center for Drug Discovery and Development, University of Notre Dame, Notre Dame, Indiana, USA.
2 Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.

PMID: 40293270 DOI: 10.1002/med.22114

Abstract

The beta isoform of 90 kDa heat shock protein (Hsp90β) plays a critical role in maintaining cellular proteostasis by assisting in the folding and refolding of proteins, which is essential for both normal cellular function and stress response. It is constitutively expressed in mammalian cells, differentiating it from the inducible Hsp90α isoform. Hsp90β's involvement in diverse cellular processes, such as signal transduction, cell cycle control, and Apoptosis, underscores its significant role in various diseases, including Cancer and neurodegenerative disorders. The isoform-specific functions of Hsp90β and its interaction with unique client proteins make it a promising target for therapeutic intervention, particularly in the development of selective inhibitors that avoid the adverse effects observed with pan-Hsp90 inhibitors. This review delves into the structural and functional intricacies of Hsp90β, its role in disease, and the potential for selective drug development.

Keywords

Hsp90 beta; drug discovery; isoform selectivity; structure‐based drug design.

Name
Email *

	Sorry, but the email address you supplied was invalid.