ArticleNature communications2022
Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 82 citations in OpenAlex.
- A design approach for bitopic kinase inhibitors.Nature · 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
- 4-Anilinoquinazoline carbamate derivatization as a platform for prodrug design and localized drug delivery.Bioorganic chemistry · 2026Article
- Mutant-Selective Binding ofInternational journal of molecular sciences · 2026Article
- Endophytic Aspergillus glaucus as a novel epothilone B producer: Antiproliferative activity and in silico analysis.Applied microbiology and biotechnology · 2026Article
- Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.bioRxiv : the preprint server for biology · 2026Article
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- Adaptation of plateau frog peptide: From antimicrobial to angiogenic and proliferative functions.Journal of advanced research · 2026Article
- Imidazole-[1,5‑ACS omega · 2026Article
- Conformational dynamics in insulin receptor kinase reveal a type III allosteric pocket.Protein science : a publication of the Protein Society · 2026Article
- Article
- Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting.ACS medicinal chemistry letters · 2026Article
- Comparative profiling of osimertinib and fourth-generation EGFR inhibitors on EGFR-mutant proteins and cell lines.Frontiers in oncology · 2026Article
- Steric disruption of EGFR oligomerization overcomes therapy resistance in non-small cell lung cancer.Science advances · 2025Article
- Resistance to Allosteric Inhibitors.Journal of molecular biology · 2025Review
- Selective Identification of Allosteric Inhibitors and Co-Drug Combinations Targeting Kinases by Using a Nanopore Tweezer Approach.ACS nano · 2025Article
- Profiling and Optimizing Targeted Covalent Inhibitors through EGFR-Guided Studies.Journal of medicinal chemistry · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Lung cancer is frequently caused by activating mutations in the epidermal growth factor receptor (EGFR). Allosteric EGFR inhibitors offer promise as the next generation of therapeutics, as they are unaffected by common ATP-site resistance mutations and synergize with the drug osimertinib. Here, we examine combinations of ATP-competitive and allosteric inhibitors to better understand the molecular basis for synergy. We identify a subset of irreversible EGFR inhibitors that display positive binding cooperativity and synergy with the allosteric inhibitor JBJ-04-125-02 in several EGFR variants. Structural analysis of these complexes reveals conformational changes occur mainly in the phosphate-binding loop (P-loop). Mutation of F723 in the P-loop reduces cooperative binding and synergy, supporting a mechanism in which F723-mediated contacts between the P-loop and the allosteric inhibitor are critical for synergy. These structural and mechanistic insights will aid in the identification and development of additional inhibitor combinations with potential clinical value.
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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.