Discovery of a Potent c‑MET Inhibitor for Non-Small Cell Lung Cancer Treatment by AI-Based and Docking-Based Virtual Screening.

The dysregulation of the mesenchymal-epithelial transition factor (c-MET) signaling pathway is linked to the development and drug resistance of non-small cell lung cancer (NSCLC), highlighting the need for small-molecule inhibitors targeting c-MET. In this study, we identified six potential c-MET inhibitors from a compound library using structure-based and AI-based virtual screening. Four compounds demonstrated c-MET inhibitory activity, with compound exhibiting potent inhibition at an IC of 40.1 nM. Further studies showed that compound effectively inhibited NSCLC cell proliferation, comparable to that of positive controls. ADMET predictions indicate favorable drug-like properties, suggesting its potential as a novel c-MET inhibitor. Molecular dynamics simulations revealed that compound stabilizes its conformation through interactions with Ala1221, Pro1158, and Lys1110, providing valuable insights for further drug development.