ArticleMedChemComm2018
Molecular insights into the interaction of Hsp90 with allosteric inhibitors targeting the C-terminal domain.
Article in MedChemComm, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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
11 citing papers in PubMed.
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Insights into the Allosteric Regulation of Human Hsp90 Revealed by NMR Spectroscopy.Biomolecules · 2024Review
- Computational approaches for the design of modulators targeting protein-protein interactions.Expert opinion on drug discovery · 2023Review
- Recent advances toward the development of Hsp90 C-terminal inhibitors.Bioorganic & medicinal chemistry letters · 2023Review
- HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).Oncology reports · 2023Review
- 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
- Structure-Activity Relationships of Benzothiazole-Based Hsp90 C-Terminal-Domain Inhibitors.Pharmaceutics · 2021Article
- Synthesis of paramagnetic ligands that target the C-terminal binding site of Hsp90.Bioorganic & medicinal chemistry letters · 2020Article
- A Chemical Biology Approach to the Chaperome in Cancer-HSP90 and Beyond.Cold Spring Harbor perspectives in biology · 2020Review
- Allosteric Regulation at the Crossroads of New Technologies: Multiscale Modeling, Networks, and Machine Learning.Frontiers in molecular biosciences · 2020Review
- KU-596 decreases mitochondrial superoxide and improves bioenergetics following downregulation of manganese superoxide dismutase in diabetic sensory neurons.Experimental neurology · 2019Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Unique to targeting the C-terminal domain of Hsp90 (C-Hsp90) is the ability to uncouple the cytotoxic and cytoprotective outcomes of Hsp90 modulation. After the identification of novobiocin as a C-Hsp90 interacting ligand a diverse gamut of novologues emerged, from which KU-32 and KU-596 exhibited strong neuroprotective activity. However, further development of these ligands is hampered by the difficulty to obtain structural information on their complexes with Hsp90. Using saturation transfer difference (STD) NMR spectroscopy, we found that the primary binding epitopes of KU-32 and KU596 map at the ring systems of the ligands and specifically the coumarin and biphenyl structures, respectively. Based on both relative and absolute STD effects, we identified KU-596 sites that can be explored to design novel third-generation novologues. In addition, chemical shift perturbations obtained by methyl-TROSY reveal that novologues bind at the cryptic, C-Hsp90 ATP-binding pocket and produce global, long-range structural rearrangements to dimeric Hsp90.
Identifiers
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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.