ArticleJournal of medicinal chemistry2021
An Exploration of Chemical Properties Required for Cooperative Stabilization of the 14-3-3 Interaction with NF-κB-Utilizing a Reversible Covalent Tethering Approach.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- Modulation of the 14-3-3σ/C-RAF "Auto"inhibited Complex by Molecular Glues.Journal of the American Chemical Society · 2026Article
- Mapping the global landscape of molecular glues in drug discovery: a bibliometric analysis from 2010 to 2024.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Hepatoprotective evaluation of benzoylated emodin derivatives: Integrating bioinformatics andBioMedicine · 2026Article
- Epoxy tetrahydrophthalimides as potential bioactive agents: synthesis and computational study.Pest management science · 2025Article
- Nondegradative Synthetic Molecular Glues Enter the Clinic.ChemMedChem · 2025Review
- 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization.Chembiochem : a European journal of chemical biology · 2024Review
- A simple method for developing lysine targeted covalent protein reagents.Nature communications · 2023Article
- Protein-protein interactions: developing small-molecule inhibitors/stabilizers through covalent strategies.Trends in pharmacological sciences · 2023Review
- Tracking the mechanism of covalent molecular glue stabilization using native mass spectrometry.Chemical science · 2023Article
- Reversible Dual-Covalent Molecular Locking of the 14-3-3/ERRγ Protein-Protein Interaction as a Molecular Glue Drug Discovery Approach.Journal of the American Chemical Society · 2023Article
- Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment.Acta pharmaceutica Sinica. B · 2022Review
- Towards identification of protein-protein interaction stabilizersRSC chemical biology · 2022Article
- miR-203, fine-tunning neuroinflammation by juggling different components of NF-κB signaling.Journal of neuroinflammation · 2022Article
- Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains.Biophysical journal · 2022Article
- Contemporary biophysical approaches for studying 14-3-3 protein-protein interactions.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-protein modulation has emerged as a proven approach to drug discovery. While significant progress has been gained in developing protein-protein interaction (PPI) inhibitors, the orthogonal approach of PPI stabilization lacks established methodologies for drug design. Here, we report the systematic ″bottom-up″ development of a reversible covalent PPI stabilizer. An imine bond was employed to anchor the stabilizer at the interface of the 14-3-3/p65 complex, leading to a molecular glue that elicited an 81-fold increase in complex stabilization. Utilizing protein crystallography and biophysical assays, we deconvoluted how chemical properties of a stabilizer translate to structural changes in the ternary 14-3-3/p65/molecular glue complex. Furthermore, we explore how this leads to high cooperativity and increased stability of the complex.
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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.