ReviewChemistry & biology2013
Developing irreversible inhibitors of the protein kinase cysteinome.
Review in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 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
259 citing papers in PubMed, 659 citations in OpenAlex.
- A lysis-derived PMSF and orthovanadate oxidant defines a distinct cysteine-engagement profile.Cell chemical biology · 2026Article
- Targeting Kinase Signaling in Glioblastoma: Structural Optimization, Blood-Brain Barrier Dynamics and Combinatorial Translational Strategies.International journal of molecular sciences · 2026Review
- Synthesis of 1,3-Disubstituted 3-Azabicyclo[3.2.0]heptane Libraries for Fragment-Based Drug Discovery.Organic letters · 2026Article
- Three Thiol-Reactive Reagents drive Synergistic Lethality in Glioblastoma cells.Research square · 2026Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease.Journal of the American Chemical Society · 2026Article
- A Synergistic Inhibitor Development Strategy Against Human UDP-Galactose-4-Epimerase.Angewandte Chemie (International ed. in English) · 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
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease ACTMAP.bioRxiv : the preprint server for biology · 2026Article
- Targeting the JNK Gatekeepers: Structural Evolution and Medicinal Chemistry of MKK4 and MKK7 Inhibitors.Molecules (Basel, Switzerland) · 2026Review
- Research progress of small molecule protein kinase inhibitors (SMKIs) in the treatment of colorectal cancer: mechanism, application, and future prospects.Frontiers in pharmacology · 2026Review
- Cysteine-enabled cleavability to advance cross-linking mass spectrometry for global analysis of endogenous protein-protein interactions.Nature communications · 2025Article
- Tryptoline Stereoprobe Elaboration Identifies Inhibitors of the GRPEL1-HSPA9 Chaperone Complex.bioRxiv : the preprint server for biology · 2025Article
- Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation ofAntimicrobial agents and chemotherapy · 2025Article
- Human PTGR2 Inactivation Alters Eicosanoid Metabolism and Cytokine Response of Inflammatory Macrophages.ACS chemical biology · 2025Article
- Advances in sulfonyl exchange chemical biology: expanding druggable target space.Chemical science · 2025Review
- Kinase-Targeted Therapies for Glioblastoma.International journal of molecular sciences · 2025Review
- Probing the Effect of Protein and Inhibitor Conformational Flexibility on the Reaction of Rocelitinib-Like Covalent Inhibitors of Epidermal Growth Factor Receptor. A Quantum Mechanics/Molecular Mechanics Study.Journal of chemical information and modeling · 2025Article
- Sulphostin-inspired N-phosphonopiperidones as selective covalent DPP8 and DPP9 inhibitors.Nature communications · 2025Article
- Article
199 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
7 authors at 5 institutions in 4 countries.
Funding
Abstract
Protein kinases are a large family of approximately 530 highly conserved enzymes that transfer a γ-phosphate group from ATP to a variety of amino acid residues, such as tyrosine, serine, and threonine, that serves as a ubiquitous mechanism for cellular signal transduction. The clinical success of a number of kinase-directed drugs and the frequent observation of disease causing mutations in protein kinases suggest that a large number of kinases may represent therapeutically relevant targets. To date, the majority of clinical and preclinical kinase inhibitors are ATP competitive, noncovalent inhibitors that achieve selectivity through recognition of unique features of particular protein kinases. Recently, there has been renewed interest in the development of irreversible inhibitors that form covalent bonds with cysteine or other nucleophilic residues in the ATP-binding pocket. Irreversible kinase inhibitors have a number of potential advantages including prolonged pharmacodynamics, suitability for rational design, high potency, and ability to validate pharmacological specificity through mutation of the reactive cysteine residue. Here, we review recent efforts to develop cysteine-targeted irreversible protein kinase inhibitors and discuss their modes of recognizing the ATP-binding pocket and their biological activity profiles. In addition, we provided an informatics assessment of the potential "kinase cysteinome" and discuss strategies for the efficient development of new covalent inhibitors.
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.