ArticleNature communications2020
Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein-protein interactions.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Protein-Protein Interaction Stabilizers from MD Simulation-Derived Pharmacophores.Journal of chemical information and modeling · 2026Article
- Neurological Effects ofNutrients · 2026Article
- Article
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Modulation of the 14-3-3σ/C-RAF "Auto"inhibited Complex by Molecular Glues.Journal of the American Chemical Society · 2026Article
- Stabilization of Native Protein-Protein Interactions with Molecular Glues: A 14-3-3 Case Study.Accounts of chemical research · 2025Article
- Cooperative Free Energy: Induced Protein-Protein Interactions and Cooperative Solvation in Ternary Complexes.Journal of chemical theory and computation · 2025Article
- Dual-protein embedding-based graph model with dynamic attention for interaction prediction.Briefings in bioinformatics · 2025Article
- Prediction of protein-protein interaction based on interaction-specific learning and hierarchical information.BMC biology · 2025Article
- Study on Phosphorus Compound/Catechol-Catalyzed Dehydrative Amidation and Its Database Development for Machine Learning.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.Nature communications · 2025Article
- Modulation of Protein-Protein Interactions with Molecular Glues in a Synthetic Condensate Platform.Journal of the American Chemical Society · 2025Article
- New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.Signal transduction and targeted therapy · 2024Review
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.bioRxiv : the preprint server for biology · 2024Article
- Fragment-Based Interrogation of the 14-3-3/TAZ Protein-Protein Interaction.Biochemistry · 2024Article
- 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization.Chembiochem : a European journal of chemical biology · 2024Review
- Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues.SLAS discovery : advancing life sciences R & D · 2024Article
- Molecular glues for protein-protein interactions: Progressing toward a new dream.Cell chemical biology · 2024Review
- Biophysical Assays for Investigating Modulators of Macromolecular Complexes: An Overview.ACS omega · 2024Review
- How Do Molecular Tweezers Bind to Proteins? Lessons from X-ray Crystallography.Molecules (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The systematic stabilization of protein-protein interactions (PPI) has great potential as innovative drug discovery strategy to target novel and hard-to-drug protein classes. The current lack of chemical starting points and focused screening opportunities limits the identification of small molecule stabilizers that engage two proteins simultaneously. Starting from our previously described virtual screening strategy to identify inhibitors of 14-3-3 proteins, we report a conceptual molecular docking approach providing concrete entries for discovery and rational optimization of stabilizers for the interaction of 14-3-3 with the carbohydrate-response element-binding protein (ChREBP). X-ray crystallography reveals a distinct difference in the binding modes between weak and general inhibitors of 14-3-3 complexes and a specific, potent stabilizer of the 14-3-3/ChREBP complex. Structure-guided stabilizer optimization results in selective, up to 26-fold enhancement of the 14-3-3/ChREBP interaction. This study demonstrates the potential of rational design approaches for the development of selective PPI stabilizers starting from weak, promiscuous PPI inhibitors.
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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.