ArticleChemical science2018
L718Q mutant EGFR escapes covalent inhibition by stabilizing a non-reactive conformation of the lung cancer drug osimertinib.
Article in Chemical science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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.
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Who cites it
38 citing papers in PubMed.
- Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity.Cancer cell · 2022Trial
- Osimertinib's Proton-Catalyzed, Pseudoconcerted EGFR Inhibition Guides Next-Generation Inhibitor Design.Journal of chemical information and modeling · 2026Article
- The Effects of Variant Allele Frequency for EGFR Mutation on Early Tumor Shrinkage and Deepness of Response to Osimertinib in Patients with Metastatic Non-Small Cell Lung Cancer: An Exploratory Analysis.Journal of clinical medicine · 2026Article
- 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
- Size-Dependent Target Engagement of Covalent Probes.Journal of medicinal chemistry · 2025Article
- L858R/L718Q and L858R/L792H Mutations of EGFR Inducing Resistance Against Osimertinib by Forming Additional Hydrogen Bonds.Proteins · 2025Article
- Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics.Cancers · 2025Review
- QM/MM Simulations of Afatinib-EGFR Addition: The Role of β-Dimethylaminomethyl Substitution.Journal of chemical theory and computation · 2024Article
- Recent Development in the Search for Epidermal Growth Factor Receptor (EGFR) Inhibitors based on the Indole Pharmacophore.Current topics in medicinal chemistry · 2024Review
- Molecular Determinants of EphA2 and EphB2 Antagonism Enable the Design of Ligands with Improved Selectivity.Journal of chemical information and modeling · 2023Article
- EGFR-T790M Mutation-Derived Interactome Rerouted EGFR Translocation Contributing to Gefitinib Resistance in Non-Small Cell Lung Cancer.Molecular & cellular proteomics : MCP · 2023Article
- Article
- Drug Design in the Exascale Era: A Perspective from Massively Parallel QM/MM Simulations.Journal of chemical information and modeling · 2023Review
- Mechanistic Modeling of Lys745 Sulfonylation in EGFR C797S Reveals Chemical Determinants for Inhibitor Activity and Discriminates Reversible from Irreversible Agents.Journal of chemical information and modeling · 2023Article
- Emerging strategies to overcome resistance to third-generation EGFR inhibitors.Journal of hematology & oncology · 2022Review
- Michael acceptor molecules in natural products and their mechanism of action.Frontiers in pharmacology · 2022Review
- Identification of potential key molecular biomarkers in lung adenocarcinoma by bioinformatics analysis.Translational cancer research · 2022Article
- Exploration of the structural requirements of Aurora Kinase B inhibitors by a combined QSAR, modelling and molecular simulation approach.Scientific reports · 2021Article
- Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors.Innovation (Cambridge (Mass.)) · 2021Review
- Tuning Proton Transfer Thermodynamics in SARS-CoV-2 Main Protease: Implications for Catalysis and Inhibitor Design.The journal of physical chemistry letters · 2021Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Osimertinib is a third-generation inhibitor approved for the treatment of non-small cell lung cancer. It overcomes resistance to first-generation inhibitors by incorporating an acrylamide group which alkylates Cys797 of EGFR T790M. The mutation of a residue in the P-loop (L718Q) was shown to cause resistance to osimertinib, but the molecular mechanism of this process is unknown. Here, we investigated the inhibitory process for EGFR T790M (susceptible to osimertinib) and EGFR T790M/L718Q (resistant to osimertinib), by modelling the chemical step (
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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.