ArticleJournal of the American Chemical Society2022
Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα.
Article in Journal of the American Chemical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Antitumor Activity of s-Triazine Derivatives: A Systematic Review.Molecules (Basel, Switzerland) · 2023Pooled it
- Multitargeted comparative evaluation suggests 2-Aoeobenoxmide shows favourable in silico binding compared to Tucatinib against ERα, HER2, AKT1, EGFR, and PIK3CA in breast cancer.Scientific reports · 2026Article
- First-in-Class Covalent Inhibitors of PFKFB3: Discovery and Characterization in PDAC Models.Journal of medicinal chemistry · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Targeting a Unique Cysteine Residue to Achieve Isoform-Selective Inhibition of the Proline Biosynthetic Enzyme Pyrroline-5-Carboxylate Reductase 2.ACS chemical biology · 2026Article
- Inhibiting Mrt4-rRNA interaction with fumaramidmycin-based derivatives as an antifungal strategy.Nature communications · 2026Article
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
- Profiling and Optimizing Targeted Covalent Inhibitors through EGFR-Guided Studies.Journal of medicinal chemistry · 2025Article
- Isoetin from Isoetaceae Exhibits Superior Pentatransferase Inhibition in Breast Cancer: Comparative Computational Profiling with FDA-Approved Tucatinib.Pharmaceuticals (Basel, Switzerland) · 2025Article
- An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes.Nature chemical biology · 2025Article
- Article
- Rapid, potent, and persistent covalent chemical probes to deconvolute PI3Kα signaling.Chemical science · 2024Article
- Application of Fluorescence- and Bioluminescence-Based Biosensors in Cancer Drug Discovery.Biosensors · 2024Review
- Cardiovascular toxicity of Bruton tyrosine kinase inhibitors: forget about selectivity but watch the clock.Blood advances · 2024Article
- Targeted Covalent Inhibitors in Drug Discovery, Chemical Biology and Beyond.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Expanding the ligandable proteome by paralog hopping with covalent probes.bioRxiv : the preprint server for biology · 2024Article
- A high affinity pan-PI3K binding module supports selective targeted protein degradation of PI3Kα.Chemical science · 2024Article
- Structural insights into the interaction of three Y-shaped ligands with PI3Kα.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes.Journal of medicinal chemistry · 2023Review
- Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases.Journal of chemical information and modeling · 2023Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Covalent protein kinase inhibitors exploit currently noncatalytic cysteines in the adenosine 5'-triphosphate (ATP)-binding site via electrophiles directly appended to a reversible-inhibitor scaffold. Here, we delineate a path to target solvent-exposed cysteines at a distance >10 Å from an ATP-site-directed core module and produce potent covalent phosphoinositide 3-kinase α (PI3Kα) inhibitors. First, reactive warheads are used to reach out to Cys862 on PI3Kα, and second, enones are replaced with druglike warheads while linkers are optimized. The systematic investigation of intrinsic warhead reactivity (
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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.