ArticleJournal of the American Chemical Society2012
Selective targeting of distinct active site nucleophiles by irreversible SRC-family kinase inhibitors.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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.
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
32 citing papers in PubMed, 97 citations in OpenAlex.
- SuFEx chemistry for nucleosides, nucleotides, and nucleic acids.RSC chemical biology · 2026Review
- Asciminib stands out as the superior tyrosine kinase inhibitor to combine with anti-CD20 monoclonal antibodies for the treatment of CD20Haematologica · 2024Article
- Sulfonylation of RNA 2'-OH groups.ACS central science · 2023Article
- Sulfur(VI) fluorides as tools in biomolecular and medicinal chemistry.Organic & biomolecular chemistry · 2023Review
- Sulfur fluoride exchange.Nature reviews. Methods primers · 2023Article
- 4-Aminopyrazolopyrimidine scaffold and its deformation in the design of tyrosine and serine/threonine kinase inhibitors in medicinal chemistry.RSC medicinal chemistry · 2022Review
- Validation of an Allosteric Binding Site of Src Kinase Identified by Unbiased Ligand Binding Simulations.Journal of molecular biology · 2022Article
- Reversible lysine-targeted probes reveal residence time-based kinase selectivity.Nature chemical biology · 2022Article
- SuFExableThe Journal of organic chemistry · 2022Article
- Structural insights into the potency and selectivity of covalent pan-FGFR inhibitors.Communications chemistry · 2022Article
- Radical-mediated vicinal addition of alkoxysulfonyl/fluorosulfonyl and trifluoromethyl groups to aryl alkyl alkynes.Chemical science · 2021Article
- Article
- Click Chemistry in Proteomic Investigations.Cell · 2020Review
- Targeted and proteome-wide analysis of metabolite-protein interactions.Current opinion in chemical biology · 2020Review
- Arylfluorosulfate-Based Electrophiles for Covalent Protein Labeling: A New Addition to the Arsenal.Angewandte Chemie (International ed. in English) · 2019Review
- Direct cysteine sulfenylation drives activation of the Src kinase.Nature communications · 2018Article
- Thiophene bridged aldehydes (TBAs) image ALDH activity in cellsChemical science · 2017Article
- Irreversible Protein Labeling by Paal-Knorr Conjugation.Chembiochem : a European journal of chemical biology · 2017Article
- Palladium-Catalyzed Fluorosulfonylvinylation of Organic Iodides.Angewandte Chemie (International ed. in English) · 2017Article
- Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions.Journal of medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Src-family tyrosine kinases play pivotal roles in human physiology and disease, and several drugs that target members of this family are in clinical use. None of these drugs appear to discriminate among closely related kinases. However, assessing their selectivity toward endogenous kinases in living cells remains a significant challenge. Here, we report the design of two Src-directed chemical probes, each consisting of a nucleoside scaffold with a 5'-electrophile. A 5'-fluorosulfonylbenzoate (1) reacts with the conserved catalytic lysine (Lys295) and shows little discrimination among related kinases. By contrast, a 5'-vinylsulfonate (2) reacts with a poorly conserved, proximal cysteine (Cys277) found in three Src-family and six unrelated kinases. Both 1 and 2 bear an alkyne tag and efficiently label their respective endogenous kinase targets in intact cells. Using 1 as a competitive probe, we determined the extent to which ponatinib, a clinical Bcr-Abl inhibitor, targets Src-family kinases. Remarkably, while ponatinib had little effect on endogenous Fyn or Src, it potently blocked the critical T-cell kinase, Lck. Probes 1 and 2 thus enable competitive profiling versus distinct kinase subsets in living cells.
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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.