ArticleProceedings of the National Academy of Sciences of the United States of America2011
Discovery and structural characterization of a small molecule 14-3-3 protein-protein interaction inhibitor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 107 citations in OpenAlex.
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.Nature communications · 2025Article
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.bioRxiv : the preprint server for biology · 2024Article
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex.Open biology · 2024Article
- Usnic Acid Targets 14-3-3 Proteins and Suppresses Cancer Progression by Blocking Substrate Interaction.JACS Au · 2024Article
- Optimizing Phosphopeptide Structures That Target 14-3-3ε in Cutaneous Squamous Cell Carcinoma.ACS omega · 2024Article
- A Pan-Respiratory Antiviral Chemotype Targeting a Host Multi-Protein Complex.bioRxiv : the preprint server for biology · 2023Article
- Optimizing Phosphopeptide Structures That Target 14-3-3ε in Cutaneous Squamous Cell Carcinoma.bioRxiv : the preprint server for biology · 2023Article
- Structural insights into the functional roles of 14-3-3 proteins.Frontiers in molecular biosciences · 2022Review
- Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis.Nature cancer · 2022Article
- Exploring the Binding Mechanism of a Supramolecular Tweezer CLR01 to 14-3-3σ ProteinFrontiers in chemistry · 2022Article
- 14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases.Trends in pharmacological sciences · 2021Review
- Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein-protein interactions.Nature communications · 2020Article
- The effect of an engineered ATCUN motif on the structure and biophysical properties of the SH3 domain of c-Src tyrosine kinase.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
- Discovery of Small-Molecule Stabilizers of 14-3-3 Protein-Protein Interactions via Dynamic Combinatorial Chemistry.ACS medicinal chemistry letters · 2020Article
- Review
- Growth inhibition by bacterial Cas2Em proteins expressed in mammalian cells.American journal of translational research · 2020Article
- Molecular Dynamics Investigations Suggest a Non-specific Recognition Strategy of 14-3-3σ Protein by Tweezer: Implication for the Inhibition Mechanism.Frontiers in chemistry · 2019Article
- Review
- Modulators of 14-3-3 Protein-Protein Interactions.Journal of medicinal chemistry · 2018Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The 14-3-3 family of phosphoserine/threonine-recognition proteins engage multiple nodes in signaling networks that control diverse physiological and pathophysiological functions and have emerged as promising therapeutic targets for such diseases as cancer and neurodegenerative disorders. Thus, small molecule modulators of 14-3-3 are much needed agents for chemical biology investigations and therapeutic development. To analyze 14-3-3 function and modulate its activity, we conducted a chemical screen and identified 4-[(2Z)-2-[4-formyl-6-methyl-5-oxo-3-(phosphonatooxymethyl)pyridin-2-ylidene]hydrazinyl]benzoate as a 14-3-3 inhibitor, which we termed FOBISIN (FOurteen-three-three BInding Small molecule INhibitor) 101. FOBISIN101 effectively blocked the binding of 14-3-3 with Raf-1 and proline-rich AKT substrate, 40 kD(a) and neutralized the ability of 14-3-3 to activate exoenzyme S ADP-ribosyltransferase. To provide a mechanistic basis for 14-3-3 inhibition, the crystal structure of 14-3-3ζ in complex with FOBISIN101 was solved. Unexpectedly, the double bond linking the pyridoxal-phosphate and benzoate moieties was reduced by X-rays to create a covalent linkage of the pyridoxal-phosphate moiety to lysine 120 in the binding groove of 14-3-3, leading to persistent 14-3-3 inactivation. We suggest that FOBISIN101-like molecules could be developed as an entirely unique class of 14-3-3 inhibitors, which may serve as radiation-triggered therapeutic agents for the treatment of 14-3-3-mediated diseases, such as cancer.
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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.