ArticleNature chemical biology2014
A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed.
- SuFEx chemistry for nucleosides, nucleotides, and nucleic acids.RSC chemical biology · 2026Review
- Stability-Based Proteomic Methods Add Value to Activity-Based Protein Profiling Studies.ACS chemical biology · 2026Article
- Stereoselective Covalent Targeting of BTK(C481S) and Kinases with β-Lactone Electrophiles.bioRxiv : the preprint server for biology · 2026Article
- Visualization of a Bruton's Tyrosine Kinase Inhibitor Using Fluorescence and Raman Microscopy.Analytical chemistry · 2026Article
- α-Halothioamide warheads with enhanced cysteine reactivity and specificity for covalent protein labelling.Nature communications · 2026Article
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- Discovery of Covalent Ligands with AlphaFold3.Journal of the American Chemical Society · 2026Article
- Molecular Dynamics-Guided Design and Chemoproteomic Profiling of Covalent Kinase Activity Probes.Journal of the American Chemical Society · 2026Article
- Inhibiting Mrt4-rRNA interaction with fumaramidmycin-based derivatives as an antifungal strategy.Nature communications · 2026Article
- Modular Vinyl Phosphonamidates for Cysteine-Directed Protein Targeting.Journal of the American Chemical Society · 2026Article
- Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity.Angewandte Chemie (International ed. in English) · 2026Article
- Article
- Molecular Dynamics-Guided Design and Chemoproteomic Profiling of Covalent Kinase Activity Probes.bioRxiv : the preprint server for biology · 2025Article
- Recent advances in chemical proteomics for protein profiling and targeted degradation.Current opinion in chemical biology · 2025Review
- Delineating cysteine-reactive compound modulation of cellular proteostasis processes.Nature chemical biology · 2025Article
- Integrative Multi-Omics Approaches Reveal Selectivity Profiles and Molecular Mechanisms of FIIN-2, a Covalent FGFR Inhibitor.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Functional proteoform group deconvolution reveals a broader spectrum of ibrutinib off-targets.Nature communications · 2025Article
- Discovery of DCAF16 Binders for Targeted Protein Degradation.ACS chemical biology · 2025Article
- Proteome selectivity profiling of photoaffinity probes derived from imidazopyrazine-kinase inhibitors.Communications chemistry · 2025Article
- Chemoselective Stabilized Triphenylphosphonium Probes for Capturing Reactive Carbonyl Species and Regenerating Covalent Inhibitors with Acrylamide Warheads in Cellulo.Journal of the American Chemical Society · 2025Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors.
Funding
Abstract
Kinases are principal components of signal transduction pathways and the focus of intense basic and drug discovery research. Irreversible inhibitors that covalently modify non-catalytic cysteines in kinase active sites have emerged as valuable probes and approved drugs. Many protein classes, however, have functional cysteines, and therefore understanding the proteome-wide selectivity of covalent kinase inhibitors is imperative. Here, we accomplish this objective using activity-based protein profiling coupled with quantitative MS to globally map the targets, both specific and nonspecific, of covalent kinase inhibitors in human cells. Many of the specific off-targets represent nonkinase proteins that, notably, have conserved active site cysteines. We define windows of selectivity for covalent kinase inhibitors and show that, when these windows are exceeded, rampant proteome-wide reactivity and kinase target-independent cell death conjointly occur. Our findings, taken together, provide an experimental road map to illuminate opportunities and surmount challenges for the development of covalent kinase inhibitors.
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