CH7233163 / Roche - LARVOL DELTA

Binding Thermodynamics of Fourth-Generation EGFR Inhibitors Revealed by Absolute Binding Free Energy Calculations. (PubMed, J Chem Inf Model) - "We compared the binding affinities of BLU-945, BLU-945 analogues, CH7233163 (another fourth-generation TKI), and erlotinib (a first-generation TKI) using absolute binding free energy calculations. Furthermore, we discovered that the incorporation of piperidinol and sulfone groups in BLU-945 substantially enhanced its binding capacity to EGFR mutants. Our study offers valuable theoretical insights for optimizing fourth-generation EGFR TKIs."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Discovery of the allosteric inhibitor from actinomyces metabolites to target EGFR mutant protein: molecular modeling and free energy approach. (PubMed, Sci Rep) - "Docking outcomes revealed that five compounds showed better binding affinity (- 9.074 to - 9.3 kcal/mol) than both reference drug CH7233163 (- 6.11 kcal/mol) and co-crystallized ligand Osimertinib (- 8.07 kcal/mol). Compared to the reference ligand, it also demonstrated conserved H-bond interactions with the residues MET_793 and GLN_791 with strong interaction probability. In conclusion, we have found a potential drug with no violation of the rule of three, Lipinski's rule of five, and 26 other vital parameters having great potential in medicinal and pharmaceutical industries applications and can overcome synthetic drug issues."

Journal • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • EGFR

CH7233163 overcomes osimertinib resistant EGFR-Del19/T790M/C797S mutation. (PubMed, Mol Cancer Ther) - "Furthermore, crystal structure analysis suggested that CH7233163 is a non-covalent ATP competitive inhibitor for EGFR-Del19/T790M/C797S that utilizes multiple interactions with the EGFR's αC-helix-in conformation to achieve potent inhibitory activity and mutant selectivity. Therefore, we conclude that CH7233163 is a potentially effective therapy for osimertinib resistant patients, especially in cases of EGFR-Del19/T790M/C797S."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

[VIRTUAL] CH7233163, a mutant-selective EGFR inhibitor, overcomes osimertinib resistant EGFR-T790M/C797S (AACR-II 2020) - "Consistent with this insight, CH7233163 also showed potent antitumor activity against the tumors harboring EGFR single activating-mutation (deletion 19 or L858R) and double-mutation (T790M/activating-mutation) in vitro and in vivo. These result suggested that CH723316 may become a potential therapeutics to overcome osimertinib resistance in EGFR-mutated NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • EGFR

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