ArticleNature2009
Novel mutant-selective EGFR kinase inhibitors against EGFR T790M.
Article in Nature, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 425 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
425 citing papers in PubMed, 989 citations in OpenAlex.
- Clinical Characteristics and Survival Outcomes for Non-Small-Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Double Mutations.BioMed research international · 2018Trial
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- Multiparatopic antibodies overcome tyrosine kinase inhibitor resistance by inducing lysosomal degradation of EGFR mutants.Oncogene · 2026Article
- Substrate-Derived Peptides for Selective Covalent Inhibition of Protein Tyrosine Kinases.ACS chemical biology · 2026Article
- Towards better outcomes for epidermal growth factor receptor L858R+ lung cancer patients: mutant-selective allosteric inhibitors and the potential for double-drugging.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Epidermal Growth Factor Receptor as a Model Drug Target for Scrutinizing the Status Quo in Drug Discovery and Chemical Biology.ACS bio & med chem Au · 2026Review
- Structure-based identification, phosphorylation, cyclization and engineering of a self-binding peptide carboxy-terminal to EGFR kinase domain by integrating dynamics simulation, energetics calculation and fluorescence analysis.European biophysics journal : EBJ · 2026Article
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- Resistance to EGFR Inhibitors in NSCLC: Mechanistic Insights and Emerging Therapies.International journal of molecular sciences · 2026Review
- Endotracheal and Endobronchial Metastases in Epidermal Growth Factor Receptor Exon 19 Deletion Lung Adenocarcinoma: A Case Successfully Managed with Bronchoscopic Therapy and Sequential Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.Internal medicine (Tokyo, Japan) · 2026Article
- Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.bioRxiv : the preprint server for biology · 2026Article
- Tyrosine kinase inhibitor toxicity in the treatment of non-small-cell lung cancer: A bibliometric analysis (2009-2025).Medicine · 2026Article
- Multimodal investigation of dacomitinib-calf thymus DNA binding interaction: insights from spectroscopy, thermodynamics, andRSC advances · 2026Article
- Structure-informed machine learning for drug discovery: a task-centric perspective.Briefings in bioinformatics · 2026Review
- Non-small cell lung cancer after EGFR-TKI resistance: from drug resistance mechanisms to precision interventions.Frontiers in pharmacology · 2026Review
- Role of gut microbiota metabolites against vein graft restenosis: insights from network pharmacology, molecular docking and molecular dynamic simulation.BMC medical genomics · 2025Article
- Thiazolidinedione derivatives: emerging role in cancer therapy.Molecular diversity · 2025Review
- Discovery and Characterization of Cell-Permeable Inhibitors ofACS infectious diseases · 2025Article
- Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells.bioRxiv : the preprint server for biology · 2025Article
- Innovative Amino-Functionalization of Pyrido[2,3-Pharmaceuticals (Basel, Switzerland) · 2025Article
365 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
15 authors at 5 institutions in 1 country.
Funding
Abstract
The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the development of drug-resistance mutations, including the gatekeeper T790M mutation. Strategies targeting EGFR T790M with irreversible inhibitors have had limited success and are associated with toxicity due to concurrent inhibition of wild-type EGFR. All current EGFR inhibitors possess a structurally related quinazoline-based core scaffold and were identified as ATP-competitive inhibitors of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by screening an irreversible kinase inhibitor library specifically against EGFR T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors in vitro. They are also effective in murine models of lung cancer driven by EGFR T790M. Co-crystallization studies reveal a structural basis for the increased potency and mutant selectivity of these agents. These mutant-selective irreversible EGFR kinase inhibitors may be clinically more effective and better tolerated than quinazoline-based inhibitors. Our findings demonstrate that functional pharmacological screens against clinically important mutant kinases represent a powerful strategy to identify new classes of mutant-selective kinase 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.