Exploration of small-molecule inhibitors targeting Hsp110 as novel therapeutics

Rui Zhao; Congke Zhao; Ruizhe Gao; Qinling Cai; Qianbin Li; Liqing Hu

doi:10.1016/j.drudis.2024.104287

Exploration of small-molecule inhibitors targeting Hsp110 as novel therapeutics

Drug Discov Today. 2025 Jan 3:104287. doi: 10.1016/j.drudis.2024.104287. Online ahead of print.

Authors

Rui Zhao¹, Congke Zhao², Ruizhe Gao³, Qinling Cai³, Qianbin Li⁴, Liqing Hu⁵

Affiliations

¹ Shangdong Xin Zhonglu Hospital of Traditional Chinese Medicine, Jinan 250013, Shandong, China.
² Shangdong Xin Zhonglu Hospital of Traditional Chinese Medicine, Jinan 250013, Shandong, China; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Pharmaceutical Sciences, Hunan Normal University, Changsha 410013, Hunan, China.
³ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Pharmaceutical Sciences, Hunan Normal University, Changsha 410013, Hunan, China.
⁴ Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China. Electronic address: [email protected].
⁵ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Pharmaceutical Sciences, Hunan Normal University, Changsha 410013, Hunan, China. Electronic address: [email protected].

PMID: 39756648
DOI: 10.1016/j.drudis.2024.104287

Abstract

The heat shock protein (HSP) 110 family has a key role as a unique class of molecular chaperones maintaining cellular proteostasis in eukaryotes. Abnormal activation of Hsp110 has been implicated in several diseases. Given its important role in pathogenesis, Hsp110 has become a novel drug target for disease diagnosis and targeted therapy. Thus, targeting Hsp110 or its interactions with client proteins offers new therapeutic approaches. Recent studies of small-molecule inhibitors that target Hsp110 in vitro and in vivo have yielded encouraging results. In this review, we provide an overview of novel therapeutics targeting Hsp110, mainly inhibitors of protein-protein interactions (PPIs), together with a brief discussion of the relevant challenges, opportunities, and future directions.

Keywords: heat shock protein 110; molecular chaperone; novel therapeutics; protein–protein interactions; small molecule inhibitors.

Publication types

Review