ArticleACS central science2023
A Systematic Approach to the Discovery of Protein-Protein Interaction Stabilizers.
Article in ACS central science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Covalent Stabilizers of the Interaction Between 14-3-3σ and Estrogen Receptor‑α.ACS medicinal chemistry letters · 2026Article
- Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Neo-Cysteine Molecular Glues for Targeting Mutated SMAD4 Protein.Angewandte Chemie (International ed. in English) · 2026Article
- Discovery of Dimer-Dependent Aminoacrylamide Molecular Glues for 14-3-3 Protein-Protein Interactions.ACS medicinal chemistry letters · 2026Article
- Modulation of the 14-3-3σ/C-RAF "Auto"inhibited Complex by Molecular Glues.Journal of the American Chemical Society · 2026Article
- Hydrogen-Deuterium Exchange Mass Spectrometry for Molecular Glue Characterization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Glutathione S-Transferase Pi Molecular Glue Tethers Splicing Factors and Remodels Cell Metabolism.Journal of the American Chemical Society · 2025Article
- A Complete Mechanistic Framework for Molecular Glue Characterization.Journal of the American Chemical Society · 2025Article
- Stabilization of Native Protein-Protein Interactions with Molecular Glues: A 14-3-3 Case Study.Accounts of chemical research · 2025Article
- Scaffold-hopping for molecular glues targeting the 14-3-3/ERα complex.Nature communications · 2025Article
- 14-3-3ζ allows for adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation.Molecular metabolism · 2025Article
- Nondegradative Synthetic Molecular Glues Enter the Clinic.ChemMedChem · 2025Review
- 14-3-3θ phosphorylation exacerbates alpha-synuclein aggregation and toxicity.Neurobiology of disease · 2025Article
- Next steps for targeted protein degradation.Cell chemical biology · 2025Review
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Extrapolating Lessons from Targeted Protein Degradation to Other Proximity-Inducing Drugs.ACS chemical biology · 2024Review
- Disulfide Tethering to Map Small Molecule Binding Sites Transcriptome-wide.ACS chemical biology · 2024Article
- Targeted Protein Localization by Covalent 14-3-3 Recruitment.Journal of the American Chemical Society · 2024Article
- Exploring the promise of regulator of G Protein Signaling 20: insights into potential mechanisms and prospects across solid cancers and hematological malignancies.Cancer cell international · 2024Review
- 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization.Chembiochem : a European journal of chemical biology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Dysregulation of protein-protein interactions (PPIs) commonly leads to disease. PPI stabilization has only recently been systematically explored for drug discovery despite being a powerful approach to selectively target intrinsically disordered proteins and hub proteins, like 14-3-3, with multiple interaction partners. Disulfide tethering is a site-directed fragment-based drug discovery (FBDD) methodology for identifying reversibly covalent small molecules. We explored the scope of disulfide tethering for the discovery of selective PPI stabilizers (molecular glues) using the hub protein 14-3-3σ. We screened complexes of 14-3-3 with 5 biologically and structurally diverse phosphopeptides derived from the 14-3-3 client proteins ERα, FOXO1, C-RAF, USP8, and SOS1. Stabilizing fragments were found for 4/5 client complexes. Structural elucidation of these complexes revealed the ability of some peptides to conformationally adapt to make productive interactions with the tethered fragments. We validated eight fragment stabilizers, six of which showed selectivity for one phosphopeptide client, and structurally characterized two nonselective hits and four fragments that selectively stabilized C-RAF or FOXO1. The most efficacious fragment increased 14-3-3σ/C-RAF phosphopeptide affinity by 430-fold. Disulfide tethering to the wildtype C38 in 14-3-3σ provided diverse structures for future optimization of 14-3-3/client stabilizers and highlighted a systematic method to discover molecular glues.
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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.