ReviewRSC medicinal chemistry2025
Targeted protein degradation of HSP90 and associated proteins for cancer therapy
Review in RSC medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years, heat shock protein 90 (HSP90), a widely expressed molecular chaperone, has emerged as a promising anticancer target due to its crucial role in stabilizing and regulating the functions of numerous client proteins involved in various essential cellular processes, including protein folding, signalling pathways, and activation of tumor-associated proteins. Despite extensive developments, only one HSP90 inhibitor has gained approval, reflecting the complexity of the HSP90 chaperone machinery, associated side effects, and emergence of resistance mechanisms. To overcome these limitations, researchers have focused their attention on developing targeted protein degraders (TPDs), a revolutionary therapeutic approach that selectively eliminates specific dysregulated target proteins. TPDs exploit cellular degradation pathways, including the ubiquitin-proteasome system (UPS), lysosomal pathways, and autophagy to achieve precise protein degradation. Among these strategies, proteolysis-targeting chimeras (PROTACs) as well as HEMTAC/HIM-PROTACs have emerged as prominent UPS-based technologies. PROTACs link targets to E3 ligases for proteasomal removal, where HEMTACs exploit HSP90 to drive client ubiquitination, thereby offering significant potential for cancer therapeutics. Given HSP90's role in tumor progression and considering the potential of TPDs, researchers have designed and developed various HSP90-targeting PROTACs and HEMTAC/HIM-PROTACs, which exhibits remarkable efficacy, selectivity, antiproliferative potency, and the ability to overcome drug resistance. This review highlights the structural and biological functions of HSP90, delineates the mechanistic principles underlying its degradation, and summarizes the structure-activity relationships (SARs) inlcuding the synthetic strategies employed across different HSP90-directed TPD modalities. Furthermore, the challenges and opportunities associated with the utilization of HSP90 and their client proteins in developing TPDs-based therapeutics to tackle the unmet clinical needs in cancer have been discussed.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.