ArticleJournal of the American Chemical Society2023
Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments.
Article in Journal of the American Chemical Society, 2023. 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
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
21 citing papers in PubMed.
- Covalent Stabilizers of the Interaction Between 14-3-3σ and Estrogen Receptor‑α.ACS medicinal chemistry letters · 2026Article
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Induced ubiquitination of the partially disordered estrogen receptor alpha via a 14-3-3 directed molecular glue-PROTAC.Nature communications · 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
- Article
- 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
- Screening of potential oxidative stress-related biomarkers and therapeutic drugs in rheumatoid arthritis based on integrative bioinformatics, machine learning, and molecular dynamics simulations.Frontiers in molecular biosciences · 2026Article
- Clues for glues: from serendipity to nature's blueprints in degrader discovery.Essays in biochemistry · 2025Review
- 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
- Artificial Intelligence in Molecular Optimization: Current Paradigms and Future Frontiers.International journal of molecular sciences · 2025Review
- Research advancements in molecular glues derived from natural product scaffolds: Chemistry, targets, and molecular mechanisms.Chinese herbal medicines · 2025Review
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.Signal transduction and targeted therapy · 2024Review
- Extrapolating Lessons from Targeted Protein Degradation to Other Proximity-Inducing Drugs.ACS chemical biology · 2024Review
- GRespiratory research · 2024Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
The stabilization of protein-protein interactions (PPIs) has emerged as a promising strategy in chemical biology and drug discovery. The identification of suitable starting points for stabilizing native PPIs and their subsequent elaboration into selective and potent molecular glues lacks structure-guided optimization strategies. We have previously identified a disulfide fragment that stabilized the hub protein 14-3-3σ bound to several of its clients, including ERα and C-RAF. Here, we show the structure-based optimization of the nonselective fragment toward selective and highly potent small-molecule stabilizers of the 14-3-3σ/ERα complex. The more elaborated molecular glues, for example, show no stabilization of 14-3-3σ/C-RAF up to 150 μM compound. Orthogonal biophysical assays, including mass spectrometry and fluorescence anisotropy, were used to establish structure-activity relationships. The binding modes of 37 compounds were elucidated with X-ray crystallography, which further assisted the concomitant structure-guided optimization. By targeting specific amino acids in the 14-3-3σ/ERα interface and locking the conformation with a spirocycle, the optimized covalent stabilizer
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.