ArticleACS medicinal chemistry letters2020
Complex Crystal Structures of EGFR with Third-Generation Kinase Inhibitors and Simultaneously Bound Allosteric Ligands.
Article in ACS medicinal chemistry letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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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
21 citing papers in PubMed, 49 citations in OpenAlex.
- 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
- Mutant-Selective Binding ofInternational journal of molecular sciences · 2026Article
- Allosteric PROTACs: Expanding the Horizon of Targeted Protein Degradation.Journal of the American Chemical Society · 2026Review
- Covalent Alkynylpyridopyrimidinones Targeting Cysteine 775 of the Epidermal Growth Factor Receptor Overcome Resistance to Current Therapies.Journal of medicinal chemistry · 2026Article
- A Predictive Model for Thiol Reactivity ofJournal of medicinal chemistry · 2025Article
- Late-stage modification of complex drug: Base-controlled Pd-catalyzed regioselective synthesis and bioactivity of arylated osimertinibs.Science advances · 2024Article
- Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.Communications chemistry · 2024Article
- Allo-targeting of the kinase domain: Insights from in silico studies and comparison with experiments.Current opinion in structural biology · 2024Review
- Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.Research square · 2023Article
- Sitravatinib is a potential EGFR inhibitor and induce a new death phenotype in Glioblastoma.Investigational new drugs · 2023Article
- The Importance of the Pyrazole Scaffold in the Design of Protein Kinases Inhibitors as Targeted Anticancer Therapies.Molecules (Basel, Switzerland) · 2023Review
- Precision targeted therapy for EGFR mutation-positive NSCLC: Dilemmas and coping strategies.Thoracic cancer · 2023Review
- Strategy toward Kinase-Selective Drug Discovery.Journal of chemical theory and computation · 2023Article
- Structural elements that enable specificity for mutant EGFR kinase domains with next-generation small-molecule inhibitors.Methods in enzymology · 2023Article
- Quinazolinones as allosteric fourth-generation EGFR inhibitors for the treatment of NSCLC.Bioorganic & medicinal chemistry letters · 2022Article
- Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors.Nature communications · 2022Article
- Mechanism of activation and the rewired network: New drug design concepts.Medicinal research reviews · 2022Review
- Identification of Bioactive Components ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Proteome-Wide Profiling of the Covalent-Druggable Cysteines with a Structure-Based Deep Graph Learning Network.Research (Washington, D.C.) · 2022Article
- A structural perspective on targeting the RTK/Ras/MAP kinase pathway in cancer.Protein science : a publication of the Protein Society · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) and currently the gold-standard for the treatment of patients suffering from non-small cell lung cancer (NSCLC) harboring T790M-mutated epidermal growth factor receptor (EGFR). The outcome of the treatment, however, is limited by the emergence of the C797S resistance mutation. Allosteric inhibitors have a different mode of action and were developed to overcome this limitation. However, most of these innovative molecules are not effective as a single agent. Recently, mutated EGFR was successfully addressed with osimertinib combined with the allosteric inhibitor JBJ-04-125-02, but surprisingly, structural insights into their binding mode were lacking. Here, we present the first complex crystal structures of mutant EGFR in complex with third-generation inhibitors such as osimertinib and mavelertinib in the presence of simultaneously bound allosteric inhibitors. These structures highlight the possibility of further combinations targeting EGFR and lay the foundation for hybrid inhibitors as next-generation TKIs.
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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.