Exploration of small-molecule inhibitors targeting Hsp110 as novel therapeutics.

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.