Integrated computational and experimental identification of <i>N-[(1H-1,2,4-triazol-3-yl)phenyl]-1-(1H-pyrazolo[3,4-b]pyridin-3-yl)methanamide</i> as a potent and selective TIM-3 inhibitor for NSCLC immunotherapy.

ABSTRACT: Non-small cell lung cancer (NSCLC) remains a significant clinical challenge, necessitating exploration of novel therapeutic targets such as TIM-3. In this study, integrated computational and experimental methods were utilized to identify potent TIM-3 inhibitors. Survival analysis revealed a significant correlation between elevated TIM-3 expression and decreased patient survival. Structure-based virtual screening and molecular dynamics simulations identified HIT104310526 (N-[(1H-1,2,4-triazol-3-yl)phenyl]-1-(1H-pyrazolo[3,4-b]pyridin-3-yl)methanamide), a candidate exhibiting superior binding affinity and stable interactions within the TIM-3 binding pocket. MMGBSA binding free energy calculations and metadynamics further confirmed its potent binding. Physicochemical evaluations indica

SUBMITTER: Ying X 

PROVIDER: S-EPMC12183220 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature