ArticleNature chemical biology2022
Reversible lysine-targeted probes reveal residence time-based kinase selectivity.
Article in Nature chemical biology, 2022. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
- Article
- Chemical Biology 2025: Highlights From the Ch/Bi145 Course at Caltech.Chembiochem : a European journal of chemical biology · 2026Review
- Enhancing De Novo Designed Peptides and Proteins via Irreversible Covalent Isoquinolinium Capture.ACS chemical biology · 2026Article
- Mesoscale proximity labeling at chromatin leads to identification of small molecule mechanism of action.Nature communications · 2026Article
- Article
- Design, synthesis, and mechanistic evaluation of propargylated salicylaldehyde derivatives as dual apoptosis-autophagy modulator for pancreatic cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Bactericidal Activities of Copolymers Incorporating Formylphenyl Motif for Targeting Surface Proteins.ACS polymers Au · 2025Article
- COOKIE-Pro: covalent inhibitor binding kinetics profiling on the proteome scale.Nature communications · 2025Article
- Examination of a Chimeric Bis-Electrophile for Selective DNA-Protein Cross-Linking and Mechlorethamine Reveals an Unknown Source of Nitrogen Mustard Cytotoxicity.Journal of the American Chemical Society · 2025Article
- Rationally designed BCR-ABL kinase inhibitors for improved leukemia treatment via covalent and pro-/dual-drug targeting strategies.Journal of advanced research · 2025Article
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- Computational Design of Lysine Targeting Covalent Binders Using Rosetta.Journal of chemical information and modeling · 2025Article
- Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.Journal of the American Chemical Society · 2025Article
- Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Article
- Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D.Nature chemical biology · 2024Article
- Chemical Proteomics-Guided Discovery of Covalent Ligands for Cancer Proteins.Annual review of cancer biology · 2024Article
- Tying the knot with lysine.Nature reviews. Chemistry · 2024Article
- Catalyst-free late-stage functionalization to assemble α-acyloxyenamide electrophiles for selectively profiling conserved lysine residues.Communications chemistry · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
The expansion of the target landscape of covalent inhibitors requires the engagement of nucleophiles beyond cysteine. Although the conserved catalytic lysine in protein kinases is an attractive candidate for a covalent approach, selectivity remains an obvious challenge. Moreover, few covalent inhibitors have been shown to engage the kinase catalytic lysine in animals. We hypothesized that reversible, lysine-targeted inhibitors could provide sustained kinase engagement in vivo, with selectivity driven in part by differences in residence time. By strategically linking benzaldehydes to a promiscuous kinase binding scaffold, we developed chemoproteomic probes that reversibly and covalently engage >200 protein kinases in cells and mice. Probe-kinase residence time was dramatically enhanced by a hydroxyl group ortho to the aldehyde. Remarkably, only a few kinases, including Aurora A, showed sustained, quasi-irreversible occupancy in vivo, the structural basis for which was revealed by X-ray crystallography. We anticipate broad application of salicylaldehyde-based probes to proteins that lack a druggable cysteine.
Indexed as
Identifiers
What OpenQuestion holds
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.