ArticleJournal of the American Chemical Society2013
Electrophilic fragment-based design of reversible covalent kinase inhibitors.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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
77 citing papers in PubMed, 193 citations in OpenAlex.
- On-resin Heck coupling enables small-molecule ligand discovery with covalent peptide-encoded libraries.Chemical science · 2026Article
- High-throughput discovery and characterisation of pentafluorobenzene sulfonamide modifiers of Aurora A kinase.RSC chemical biology · 2026Article
- Mapping the SHP2 Allosteric Pocket With Target-Biased Covalent Fragments.Chembiochem : a European journal of chemical biology · 2026Article
- Multifaceted Small Molecules as Enzyme Modulators: Cases of Drug Discovery/Repurposing Illustrating Nature's Pragmatism.BioMed research international · 2026Review
- Characterization of the Second-Generation Covalent Fragment Library (CovLib Gen2): Thiol Reactivity Profiling and p53-Y220C Rescue.Drug design, development and therapy · 2026Article
- Advances in reversible covalent kinase inhibitors.Medicinal research reviews · 2025Review
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Exploring Extended Warheads toward Developing Cysteine-Targeted Covalent Kinase Inhibitors.Journal of chemical information and modeling · 2024Article
- Open-source electrophilic fragment screening platform to identify chemical starting points for UCHL1 covalent inhibitors.SLAS discovery : advancing life sciences R & D · 2024Article
- Fluoromethylketone-Fragment Conjugates Designed as Covalent Modifiers of EcDsbA are Atypical Substrates.ChemMedChem · 2024Article
- Identification and Evaluation of Reversible Covalent Binders to Cys55 of Bfl-1 from a DNA-Encoded Chemical Library Screen.ACS medicinal chemistry letters · 2024Article
- Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?International journal of molecular sciences · 2024Review
- Solid-Phase Compatible Silane-Based Cleavable Linker Enables Custom Isobaric Quantitative Chemoproteomics.Journal of the American Chemical Society · 2023Article
- Thiomethyltetrazines Are Reversible Covalent Cysteine Warheads Whose Dynamic Behavior can be "Switched Off"Journal of the American Chemical Society · 2023Article
- Technologies for Direct Detection of Covalent Protein-Drug Adducts.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B.eLife · 2023Article
- Nitriles: an attractive approach to the development of covalent inhibitors.RSC medicinal chemistry · 2023Review
- An update on the discovery and development of reversible covalent inhibitors.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023Review
- Advances in covalent drug discovery.Nature reviews. Drug discovery · 2022Review
- Applications of covalent chemistry in targeted protein degradation.Chemical Society reviews · 2022Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Fragment-based ligand design and covalent targeting of noncatalytic cysteines have been employed to develop potent and selective kinase inhibitors. Here, we combine these approaches, starting with a panel of low-molecular-weight, heteroaryl-susbstituted cyanoacrylamides, which we have previously shown to form reversible covalent bonds with cysteine thiols. Using this strategy, we identify electrophilic fragments with sufficient ligand efficiency and selectivity to serve as starting points for the first reported inhibitors of the MSK1 C-terminal kinase domain. Guided by X-ray co-crystal structures, indazole fragment 1 was elaborated to afford 12 (RMM-46), a reversible covalent inhibitor that exhibits high ligand efficiency and selectivity for MSK/RSK-family kinases. At nanomolar concentrations, 12 blocked activation of cellular MSK and RSK, as well as downstream phosphorylation of the critical transcription factor, CREB.
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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.