ArticleChemistry (Weinheim an der Bergstrasse, Germany)2020
Chemical Perturbation of Oncogenic Protein Folding: from the Prediction of Locally Unstable Structures to the Design of Disruptors of Hsp90-Client Interactions.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2020. 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
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.
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
29 citing papers in PubMed, 56 citations in OpenAlex.
- Design of multi-target peptide modulators for protein chaperone networks.Structure (London, England : 1993) · 2025Article
- MOLECULE: Molecular-dynamics and Optimized deep Learning for Entropy-regularized Classification and Uncertainty-aware Ligand Evaluation.Journal of chemical theory and computation · 2025Article
- Advancing Molecular Simulations: Merging Physical Models, Experiments, and AI to Tackle Multiscale Complexity.The journal of physical chemistry letters · 2025Review
- Genetic and structural insights into the functional importance of the conserved gly-met-rich C-terminal tails in bacterial chaperonins.Communications biology · 2025Article
- Modulators of the Hop-HSP90 Protein-Protein Interaction Disrupt KSHV Lytic Replication.ACS infectious diseases · 2024Article
- N-Glycosylation-Induced Pathologic Protein Conformations as a Tool to Guide the Selection of Biologically Active Small Molecules.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery.Cell reports · 2023Article
- Computational approaches for the design of modulators targeting protein-protein interactions.Expert opinion on drug discovery · 2023Review
- Emerging approaches to CDK inhibitor development, a structural perspective.RSC chemical biology · 2023Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8-9, 2022.Cell stress & chaperones · 2023Article
- Computational Epitope Prediction and Design for Antibody Development and Detection.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Synthesis and Evaluation of Small Molecule Disruptors of the Aha1/Hsp90 Complex for the Reduction of Tau Aggregation.ACS medicinal chemistry letters · 2022Article
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- Emerging of composition variations of SARS-CoV-2 spike protein and human ACE2 contribute to the level of infection:Journal of biomolecular structure & dynamics · 2022Article
- Exploration of the structural requirements of Aurora Kinase B inhibitors by a combined QSAR, modelling and molecular simulation approach.Scientific reports · 2021Article
- Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system.Nature communications · 2021Article
- The tumor suppressor folliculin inhibits lactate dehydrogenase A and regulates the Warburg effect.Nature structural & molecular biology · 2021Article
- Design and Synthesis of TRAP1 Selective Inhibitors: H-Bonding with Asn171 Residue in TRAP1 Increases Paralog Selectivity.ACS medicinal chemistry letters · 2021Article
- Structural Model for Recruitment of RIT1 to the LZTR1 E3 Ligase: Evidences from an Integrated Computational Approach.Journal of chemical information and modeling · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
Protein folding quality control in cells requires the activity of a class of proteins known as molecular chaperones. Heat shock protein-90 (Hsp90), a multidomain ATP driven molecular machine, is a prime representative of this family of proteins. Interactions between Hsp90, its co-chaperones, and client proteins have been shown to be important in facilitating the correct folding and activation of clients. Hsp90 levels and functions are elevated in tumor cells. Here, we computationally predict the regions on the native structures of clients c-Abl, c-Src, Cdk4, B-Raf and Glucocorticoid Receptor, that have the highest probability of undergoing local unfolding, despite being ordered in their native structures. Such regions represent potential ideal interaction points with the Hsp90-system. We synthesize mimics spanning these regions and confirm their interaction with partners of the Hsp90 complex (Hsp90, Cdc37 and Aha1) by Nuclear Magnetic Resonance (NMR). Designed mimics selectively disrupt the association of their respective clients with the Hsp90 machinery, leaving unrelated clients unperturbed and causing apoptosis in cancer cells. Overall, selective targeting of Hsp90 protein-protein interactions is achieved without causing indiscriminate degradation of all clients, setting the stage for the development of therapeutics based on specific chaperone:client perturbation.
Indexed as
Identifiers
What OpenQuestion holds
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.