The evolution of heat shock protein 90 C-terminal inhibitors: From novobiocin to potential clinical candidates.

Xiaosheng Jiang, Brian S J Blagg

Abstract readReview

In one paragraph

Review in Cell stress & chaperones, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

Dual Epigenetic and Chaperone Inhibition Disrupts Hypoxia Signaling and Tumor Progression in 3-D Models of Triple-Negative Breast Cancer.Research square · 2026
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Xiaosheng JiangDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.

Brian S J BlaggDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; Warren Family Research Center for Drug Discovery and Development, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: bblagg@nd.edu.

Funding

Engineering the Next Generation of Safer Hsp90 InhibitorsR01CA270147 · NCI · UNIVERSITY OF NOTRE DAME · PI Brian S J Blagg, Mark Steven Cohen · 2023 to 2026

$1.8M

NCI NIH HHS R01 CA270147

6 · The paper itself

Abstract

Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone that regulates the maturation of various client proteins. Most therapeutic studies have focused on N-terminal Hsp90 inhibitors, but these are limited by dose-escalating toxicities that are caused by induction of the heat shock response. Leonard Neckers' discovery of novobiocin as a Hsp90 C-terminal inhibitor revealed an alternative mode to Hsp90 inhibition and established the C-terminal domain (CTD) as a therapeutic target. This review highlights recent advances in Hsp90 CTD inhibition and summarizes the evolution of novobiocin-based C-terminal inhibitors. Structure-activity relationship studies are discussed, demonstrating how medicinal chemistry optimization has produced CTD modulators with selective anti-proliferative or neuroprotective activities.

Indexed as

HSP90 Heat-Shock ProteinsNovobiocinAnimalsAntineoplastic AgentsHumansNeuroprotective AgentsProtein DomainsStructure-Activity RelationshipAntineoplastic AgentsHSP90 Heat-Shock ProteinsNeuroprotective AgentsNovobiocinAnti-cancerHsp90 C-terminal domain (CTD)NeuroprotectiveNovobiocin

Identifiers

PMID41796637

DOI10.1016/j.cstres.2026.100165

PMCPMC13053691

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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.