ArticleBiochimica et biophysica acta. General subjects2017
Targeting the Hsp90 C-terminal domain to induce allosteric inhibition and selective client downregulation.
Article in Biochimica et biophysica acta. General subjects, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Heat Shock Proteins as Targets for Cancer Therapeutics.Journal of clinical medicine · 2026Review
- Breaking the bonds: targeting protein dimerization for prostate cancer therapy.Endocrinology · 2026Review
- Review
- Integrating Network Pharmacology and Experimental Validation to Explore the Effect and Mechanism ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Site-specifically Phosphorylated Hsp90C-terminal Domain Variants Provide Access to Deciphering the Chaperone Code.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Hiding in plain sight: Optimizing topoisomerase IIα inhibitors into Hsp90β selective binders.European journal of medicinal chemistry · 2024Article
- C-terminal domain dimerization in yeast Hsp90 is moderately modulated by the other domains.Biophysical journal · 2024Article
- Structural basis of the key residue W320 responsible for Hsp90 conformational change.Journal of biomolecular structure & dynamics · 2023Article
- Recent advances toward the development of Hsp90 C-terminal inhibitors.Bioorganic & medicinal chemistry letters · 2023Review
- Development of a First-in-Class Small-Molecule Inhibitor of the C-Terminal Hsp90 Dimerization.ACS central science · 2022Article
- Crystal structure of the middle and C-terminal domains of Hsp90α labeled with a coumarin derivative reveals a potential allosteric binding site as a drug target.Acta crystallographica. Section D, Structural biology · 2022Article
- Development of a High-throughput NanoBRET Screening Platform to Identify Modulators of the RAS/RAF Interaction.Molecular cancer therapeutics · 2021Article
- Structure-Activity Relationships of Benzothiazole-Based Hsp90 C-Terminal-Domain Inhibitors.Pharmaceutics · 2021Article
- Modulation of Human Hsp90α Conformational Dynamics by Allosteric Ligand Interaction at the C-Terminal Domain.Scientific reports · 2019Article
- Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity.Antimicrobial agents and chemotherapy · 2018Article
- Dihydropyridines Allosterically Modulate Hsp90 Providing a Novel Mechanism for Heat Shock Protein Co-induction and Neuroprotection.Frontiers in molecular biosciences · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInhibition of Hsp90 is desirable due to potential downregulation of oncogenic clients. Early generation inhibitors bind to the N-terminal domain (NTD) but C-terminal domain (CTD) inhibitors are a promising class because they do not induce a heat shock response. Here we present a new structural class of CTD binding molecules with a unique allosteric inhibition mechanism.
methodsA hit molecule, NSC145366, and structurally similar probes were assessed for inhibition of Hsp90 activities. A ligand-binding model was proposed indicating a novel Hsp90 CTD binding site. Client protein downregulation was also determined.
resultsNSC145366 interacts with the Hsp90 CTD and has anti-proliferative activity in tumor cell lines (GI
conclusionsA set of symmetrical scaffold molecules with bisphenol A cores induced allosteric inhibition of Hsp90. Experimental evidence and molecular modeling suggest that the binding site is independent of the CTD-ATP site and consistent with unique induction of allosteric effects. GENERAL SIGNIFICANCE: Allosteric inhibition of Hsp90 via a mechanism used by the NSC145366-based probes is a promising avenue for selective oncogenic client downregulation.
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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.