ArticleJournal of chemical information and modeling2014
Exploiting conformational dynamics in drug discovery: design of C-terminal inhibitors of Hsp90 with improved activities.
Article in Journal of chemical information and modeling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed.
- Investigation of a cryptic ligand binding site on Plasmodium falciparum Hsp90.Bioorganic & medicinal chemistry · 2025Article
- Arrestins as Possible Drug Targets.Biomolecules & therapeutics · 2025Review
- Insight into the Nucleotide Based Modulation of the Grp94 Molecular Chaperone Using Multiscale Dynamics.The journal of physical chemistry. B · 2023Article
- Synthesis and evaluation of 3'- and 4'-substituted cyclohexyl noviomimetics that modulate mitochondrial respiration.Bioorganic & medicinal chemistry · 2022Article
- In Silico Discovery and Optimisation of a Novel Structural Class of Hsp90 C-Terminal Domain Inhibitors.Biomolecules · 2022Article
- Structure-Activity Relationships of Benzothiazole-Based Hsp90 C-Terminal-Domain Inhibitors.Pharmaceutics · 2021Article
- Machine Learning Prediction of Allosteric Drug Activity from Molecular Dynamics.The journal of physical chemistry letters · 2021Article
- Comparative structural and mechanistic studies of 4-hydroxy-tetrahydrodipicolinate reductases from Mycobacterium tuberculosis and Vibrio vulnificus.Biochimica et biophysica acta. General subjects · 2021Article
- Discovery of Novel Hsp90 C-Terminal Inhibitors Using 3D-Pharmacophores Derived from Molecular Dynamics Simulations.International journal of molecular sciences · 2020Article
- Modulation of Human Hsp90α Conformational Dynamics by Allosteric Ligand Interaction at the C-Terminal Domain.Scientific reports · 2019Article
- Synthesis and evaluation of a ring-constrained Hsp90 C-terminal inhibitor that exhibits neuroprotective activity.Bioorganic & medicinal chemistry letters · 2018Article
- Discovery of new molecular entities able to strongly interfere with Hsp90 C-terminal domain.Scientific reports · 2018Article
- Therapeutic Strategies for Restoring Tau Homeostasis.Cold Spring Harbor perspectives in medicine · 2018Review
- Synthesis and Biological Evaluation of Stilbene Analogues as Hsp90 C-Terminal Inhibitors.ChemMedChem · 2017Article
- Targeting the Hsp90 C-terminal domain to induce allosteric inhibition and selective client downregulation.Biochimica et biophysica acta. General subjects · 2017Article
- Design of Allosteric Stimulators of the Hsp90 ATPase as New Anticancer Leads.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors.Chemistry (Weinheim an der Bergstrasse, Germany) · 2016Article
- Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands.Chemistry (Weinheim an der Bergstrasse, Germany) · 2015Article
- Design, synthesis and biological evaluation of biphenylamide derivatives as Hsp90 C-terminal inhibitors.European journal of medicinal chemistry · 2015Article
- Inhibition of succinate dehydrogenase by the mitochondrial chaperone TRAP1 has anti-oxidant and anti-apoptotic effects on tumor cells.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The interaction that occurs between molecules is a dynamic process that impacts both structural and conformational properties of the ligand and the ligand binding site. Herein, we investigate the dynamic cross-talk between a protein and the ligand as a source for new opportunities in ligand design. Analysis of the formation/disappearance of protein pockets produced in response to a first-generation inhibitor assisted in the identification of functional groups that could be introduced onto scaffolds to facilitate optimal binding, which allowed for increased binding with previously uncharacterized regions. MD simulations were used to elucidate primary changes that occur in the Hsp90 C-terminal binding pocket in the presence of first-generation ligands. This data was then used to design ligands that adapt to these receptor conformations, which provides access to an energy landscape that is not visible in a static model. The newly synthesized compounds demonstrated antiproliferative activity at ∼150 nM concentration. The method identified herein may be used to design chemical probes that provide additional information on structural variations of Hsp90 C-terminal binding site.
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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.