ArticleACS medicinal chemistry letters2022
Structural Basis for Inhibition of Mutant EGFR with Lazertinib (YH25448).
Article in ACS medicinal chemistry letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Cost-effectiveness analyses of amivantamab plus lazertinib and lazertinib versus osimertinib in non-small cell lung cancer with EGFR mutations.Frontiers in pharmacology · 2025Pooled it
- Subcutaneous Amivantamab and Lazertinib in PALOMA-3: Efficacy, Safety, and Administration: A Vodcast.Targeted oncology · 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
- Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting.ACS medicinal chemistry letters · 2026Article
- Clinical Pharmacokinetic Assessment of Lazertinib in Healthy Adult Participants: Effects of GSTM1 Genotype.Clinical drug investigation · 2025Article
- A comprehensive comparison of third generation epidermal growth factor receptor tyrosine kinase inhibitors in the treatment efficacy and adverse events: A Bayesian meta-analysis.Global medical genetics · 2025Article
- Profiling and Optimizing Targeted Covalent Inhibitors through EGFR-Guided Studies.Journal of medicinal chemistry · 2025Article
- Structure-Activity Relationships of Inactive-Conformation Binding EGFR Inhibitors: Linking the ATP and Allosteric Pockets.Archiv der Pharmazie · 2025Article
- Design and investigation of novel iridoid-based peptide conjugates for targeting EGFR and its mutants L858R and T790M/L858R/C797S: an in silico study.Molecular diversity · 2025Article
- Ascertaining a Structural Basis in Drug Discovery and Development.Journal of medicinal chemistry · 2025Article
- Panduratin A fromInternational journal of molecular sciences · 2025Article
- Cost-effectiveness analysis of first-line treatments for recurrent or metastatic head and neck cancer in China: an economic evaluation based on network meta-analysis.Frontiers in pharmacology · 2025Article
- Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent "Type V" Kinase Inhibitors.Journal of medicinal chemistry · 2024Article
- Demystifying Functional Parameters for Irreversible Enzyme Inhibitors.Journal of medicinal chemistry · 2024Article
- The Advent of Molecular Targeted Therapies Against Cancer. Toward Multi-Targeting Drugs Through Materials Engineering: A Possible Future Scenario.Small science · 2024Article
- Synthetic Routes and Clinical Application of Representative Small-Molecule EGFR Inhibitors for Cancer Therapy.Molecules (Basel, Switzerland) · 2024Review
- Pyrrolo[2,3-D]Pyrimidines as EGFR and VEGFR Kinase Inhibitors: A Comprehensive SAR Review.Current medicinal chemistry · 2024Review
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor.Cell chemical biology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Lazertinib (YH25448) is a novel third-generation tyrosine kinase inhibitor (TKI) developed as a treatment for EGFR mutant non-small cell lung cancer. To better understand the nature of lazertinib inhibition, we determined crystal structures of lazertinib in complex with both WT and mutant EGFR and compared its binding mode to that of structurally related EGFR TKIs. We observe that lazertinib binds EGFR with a distinctive pyrazole moiety enabling hydrogen bonds and van der Waals interactions facilitated through hydrophilic amine and hydrophobic phenyl groups, respectively. Biochemical assays and cell studies confirm that lazertinib effectively targets EGFR(L858R/T790M) and to a lesser extent HER2. The molecular basis for lazertinib inhibition of EGFR reported here highlights previously unexplored binding interactions leading to improved medicinal chemistry properties compared to clinically approved osimertinib (AZD9291) and offers novel strategies for structure-guided design of tyrosine kinase inhibitors.
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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.