ArticleJournal of the American Chemical Society2019
Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 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.
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Who cites it
177 citing papers in PubMed.
- Toward Ideal Proximity-Driven Reactions in Chemical Biology.Chembiochem : a European journal of chemical biology · 2026Review
- Covalent Stabilizers of the Interaction Between 14-3-3σ and Estrogen Receptor‑α.ACS medicinal chemistry letters · 2026Article
- On-resin Heck coupling enables small-molecule ligand discovery with covalent peptide-encoded libraries.Chemical science · 2026Article
- Substrate-Derived Peptides for Selective Covalent Inhibition of Protein Tyrosine Kinases.ACS chemical biology · 2026Article
- Covalent allosteric inhibition of AARS1 lactyltransferase.Nature communications · 2026Article
- Substrate biasing in UCHL5 proteoforms.bioRxiv : the preprint server for biology · 2026Article
- A FRET-Based Assay for Assessing Covalent Warhead Reactivity.ACS omega · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Modular Rh-Catalyzed Synthesis and Biological Profiling of Diverse Pentafluorobenzenesulfonamide Reactive Fragments.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- First-in-Class Covalent Inhibitors of PFKFB3: Discovery and Characterization in PDAC Models.Journal of medicinal chemistry · 2026Article
- Fragment-Based Design of Targeted Covalent Inhibitors: The Scope and Limitation of Linking Approaches.ChemMedChem · 2026Article
- Structural and biochemical insight into allosteric regulation of the human 2-aminoadipic semialdehyde synthase, a bifunctional enzyme involved in lysine catabolism.Research square · 2026Article
- A Synergistic Inhibitor Development Strategy Against Human UDP-Galactose-4-Epimerase.Angewandte Chemie (International ed. in English) · 2026Article
- Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.bioRxiv : the preprint server for biology · 2026Article
- α-Halothioamide warheads with enhanced cysteine reactivity and specificity for covalent protein labelling.Nature communications · 2026Article
- High-throughput discovery and characterisation of pentafluorobenzene sulfonamide modifiers of Aurora A kinase.RSC chemical biology · 2026Article
- BromoCatch: a self-labelling tag platform for protein modification and live cell imaging.Nature communications · 2026Article
- Mapping the SHP2 Allosteric Pocket With Target-Biased Covalent Fragments.Chembiochem : a European journal of chemical biology · 2026Article
- Application of a MALDI mass spectrometry assay to identify covalent fragments targeting the methyl-lysine reader protein MPP8.SLAS discovery : advancing life sciences R & D · 2026Article
- Normalizing Covalent Potency for Electrophilicity with Ligand Reactivity Efficiency.Journal of medicinal chemistry · 2026Review
117 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors.
Funding
Abstract
Covalent probes can display unmatched potency, selectivity, and duration of action; however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversible fragment screening, but such electrophilic fragments were considered nonselective and were rarely screened. We hypothesized that mild electrophiles might overcome the selectivity challenge and constructed a library of 993 mildly electrophilic fragments. We characterized this library by a new high-throughput thiol-reactivity assay and screened them against 10 cysteine-containing proteins. Highly reactive and promiscuous fragments were rare and could be easily eliminated. In contrast, we found hits for most targets. Combining our approach with high-throughput crystallography allowed rapid progression to potent and selective probes for two enzymes, the deubiquitinase OTUB2 and the pyrophosphatase NUDT7. No inhibitors were previously known for either. This study highlights the potential of electrophile-fragment screening as a practical and efficient tool for covalent-ligand discovery.
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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.