ArticleChemistry (Weinheim an der Bergstrasse, Germany)2015
Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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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.
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Who cites it
29 citing papers in PubMed, 69 citations in OpenAlex.
- Investigation of a cryptic ligand binding site on Plasmodium falciparum Hsp90.Bioorganic & medicinal chemistry · 2025Article
- How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view.Structure (London, England : 1993) · 2023Article
- Synthesis and evaluation of 3'- and 4'-substituted cyclohexyl noviomimetics that modulate mitochondrial respiration.Bioorganic & medicinal chemistry · 2022Article
- Hsp90: From Cellular to Organismal Proteostasis.Cells · 2022Review
- Development of a First-in-Class Small-Molecule Inhibitor of the C-Terminal Hsp90 Dimerization.ACS central science · 2022Article
- Machine Learning Prediction of Allosteric Drug Activity from Molecular Dynamics.The journal of physical chemistry letters · 2021Article
- Design, Synthesis and In Vitro Investigation of Novel Basic Celastrol Carboxamides as Bio-Inspired Leishmanicidal Agents Endowed with Inhibitory Activity againstBiomolecules · 2021Article
- Understanding the Hsp90Molecules (Basel, Switzerland) · 2020Article
- Investigating Cryptic Binding Sites by Molecular Dynamics Simulations.Accounts of chemical research · 2020Review
- Allosteric Regulation of Hsp90α's Activity by Small Molecules Targeting the Middle Domain of the Chaperone.iScience · 2020Article
- Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells.Chemical science · 2020Article
- Allosteric Regulation at the Crossroads of New Technologies: Multiscale Modeling, Networks, and Machine Learning.Frontiers in molecular biosciences · 2020Review
- Dynamically Shaping Chaperones. Allosteric Modulators of HSP90 Family as Regulatory Tools of Cell Metabolism in Neoplastic Progression.Frontiers in oncology · 2020Review
- Modulation of Human Hsp90α Conformational Dynamics by Allosteric Ligand Interaction at the C-Terminal Domain.Scientific reports · 2019Article
- Adapting to stress - chaperome networks in cancer.Nature reviews. Cancer · 2018Review
- Synthesis and evaluation of a ring-constrained Hsp90 C-terminal inhibitor that exhibits neuroprotective activity.Bioorganic & medicinal chemistry letters · 2018Article
- Molecular insights into the interaction of Hsp90 with allosteric inhibitors targeting the C-terminal domain.MedChemComm · 2018Article
- Effects of Inhibitors on Hsp90's Conformational Dynamics, Cochaperone and Client Interactions.Chemphyschem : a European journal of chemical physics and physical chemistry · 2018Article
- Dihydropyridines Allosterically Modulate Hsp90 Providing a Novel Mechanism for Heat Shock Protein Co-induction and Neuroprotection.Frontiers in molecular biosciences · 2018Article
- In Silico Studies in Drug Research Against Neurodegenerative Diseases.Current neuropharmacology · 2018Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Hsp90 is a molecular chaperone of pivotal importance for multiple cell pathways. ATP-regulated internal dynamics are critical for its function and current pharmacological approaches block the chaperone with ATP-competitive inhibitors. Herein, a general approach to perturb Hsp90 through design of new allosteric ligands aimed at modulating its functional dynamics is proposed. Based on the characterization of a first set of 2-phenylbenzofurans showing stimulatory effects on Hsp90 ATPase and conformational dynamics, new ligands were developed that activate Hsp90 by targeting an allosteric site, located 65 Å from the active site. Specifically, analysis of protein responses to first-generation activators was exploited to guide the design of novel derivatives with improved ability to stimulate ATP hydrolysis. The molecules' effects on Hsp90 enzymatic, conformational, co-chaperone and client-binding properties were characterized through biochemical, biophysical and cellular approaches. These designed probes act as allosteric activators of the chaperone and affect the viability of cancer cell lines for which proper functioning of Hsp90 is necessary.
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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.