ArticleNature communications2019
The transcription factor STAT5 catalyzes Mannich ligation reactions yielding inhibitors of leukemic cell proliferation.
Article in Nature communications, 2019. 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, 30 citations in OpenAlex.
- Click Reactions in Kinetic Target-Guided Synthesis: Progress in the Discovery of Inhibitors for Biological Targets.Methods and protocols · 2026Review
- Royal jelly and doxorubicin suppressed tumor cells in the xenograft model of lung cancer via the STAT3/FOXM1/ATG7 signaling pathways in athymic nude mice: a biochemical, immunohistochemically and molecular approach.Toxicology research · 2025Article
- Chemoselective seleno-click amidation in kinetic target-guided synthesis.Chemical communications (Cambridge, England) · 2024Article
- Targeted small molecule inhibitors blocking the cytolytic effects of pneumolysin and homologous toxins.Nature communications · 2024Article
- Identification and Optimization of Protein Tyrosine Phosphatase Inhibitors Via Fragment Ligation.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The Groebke-Blackburn-Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019-2023).Beilstein journal of organic chemistry · 2024Review
- Shotgun Kinetic Target-Guided Synthesis Approach Enables the Discovery of Small-Molecule Inhibitors against Pathogenic Free-Living Amoeba Glucokinases.ACS infectious diseases · 2023Article
- Going beyond Binary: Rapid Identification of Protein-Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach.Journal of medicinal chemistry · 2023Article
- Pentafluorophosphato-Phenylalanines: Amphiphilic Phosphotyrosine Mimetics Displaying Fluorine-Specific Protein Interactions.Angewandte Chemie (International ed. in English) · 2022Article
- Chemical Evolution of Antivirals Against Enterovirus D68 through Protein-Templated Knoevenagel Reactions.Angewandte Chemie (International ed. in English) · 2021Article
- Protein-Templated Hit Identification through an Ugi Four-Component Reaction*.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Recent advances in synthetic and medicinal chemistry of phosphotyrosine and phosphonate-based phosphotyrosine analogues.RSC medicinal chemistry · 2020Review
- The Selectivity of Fosfosal for STAT5b over STAT5a is Mediated by Arg566 in the Linker Domain.Chembiochem : a European journal of chemical biology · 2020Article
- Stafia-1: a STAT5a-Selective Inhibitor Developed via Docking-Based Screening of in Silico O-Phosphorylated Fragments.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Direct Targeting Options for STAT3 and STAT5 in Cancer.Cancers · 2019Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-templated fragment ligations have been established as a powerful method for the assembly and detection of optimized protein ligands. Initially developed for reversible ligations, the method has been expanded to irreversible reactions enabling the formation of super-additive fragment combinations. Here, protein-induced Mannich ligations are discovered as a biocatalytic reaction furnishing inhibitors of the transcription factor STAT5. STAT5 protein catalyzes multicomponent reactions of a phosphate mimetic, formaldehyde, and 1H-tetrazoles yielding protein ligands with greatly increased binding affinity and ligand efficiency. Reactions are induced under physiological conditions selectively by native STAT5 but not by other proteins. Formation of ligation products and (auto-)inhibition of the reaction are quantified and the mechanism is investigated. Inhibitors assembled by STAT5 block specifically the phosphorylation of this protein in a cellular model of acute myeloid leukemia (AML), DNA-binding of STAT5 dimers, expression of downstream targets of the transcription factor, and the proliferation of cancer cells in mice.
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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.