ArticleNature cancer2022
An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 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
78 citing papers in PubMed, 150 citations in OpenAlex.
- 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
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Mutant-Selective Binding ofInternational journal of molecular sciences · 2026Article
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging.Cell · 2026Article
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- JIN-A02, a Mutant-Selective Fourth-Generation EGFR Inhibitor, Overcomes C797S-Mediated Resistance and Demonstrates Intracranial Activity in NSCLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The resistance landscape of EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer: molecular mechanisms and novel therapeutic strategies.Translational lung cancer research · 2026Review
- Epidermal growth factor receptor tyrosine kinase inhibitor for the treatment of non-small cell lung cancer in the past 30 years (1997-2026).Chinese medical journal · 2026Review
- TAS3351 is a brain penetrable EGFR-TKI that overcomes T790M and C797S resistant mutations.Communications medicine · 2026Article
- Imidazole-[1,5‑ACS omega · 2026Article
- Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting.ACS medicinal chemistry letters · 2026Article
- Non-small cell lung cancer after EGFR-TKI resistance: from drug resistance mechanisms to precision interventions.Frontiers in pharmacology · 2026Review
- Comparative profiling of osimertinib and fourth-generation EGFR inhibitors on EGFR-mutant proteins and cell lines.Frontiers in oncology · 2026Article
- Immune checkpoint inhibitor-based combinatory and alternative strategies for immune treatment of lung cancers.Frontiers in immunology · 2026Review
- Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC - mechanisms and evolving treatment approaches.Nature reviews. Clinical oncology · 2026Review
- Steric disruption of EGFR oligomerization overcomes therapy resistance in non-small cell lung cancer.Science advances · 2025Article
- Fourth-generation EGFR-TKI to overcome C797S mutation: past, present, and future.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge.Journal of molecular biology · 2025Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 4 institutions in 3 countries.
Funding
Abstract
Epidermal growth factor receptor (EGFR) therapy using small-molecule tyrosine kinase inhibitors (TKIs) is initially efficacious in patients with EGFR-mutant lung cancer, although drug resistance eventually develops. Allosteric EGFR inhibitors, which bind to a different EGFR site than existing ATP-competitive EGFR TKIs, have been developed as a strategy to overcome therapy-resistant EGFR mutations. Here we identify and characterize JBJ-09-063, a mutant-selective allosteric EGFR inhibitor that is effective across EGFR TKI-sensitive and resistant models, including those with EGFR T790M and C797S mutations. We further uncover that EGFR homo- or heterodimerization with other ERBB family members, as well as the EGFR L747S mutation, confers resistance to JBJ-09-063, but not to ATP-competitive EGFR TKIs. Overall, our studies highlight the potential clinical utility of JBJ-09-063 as a single agent or in combination with EGFR TKIs to define more effective strategies to treat EGFR-mutant lung cancer.
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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.