Molecular Dynamics-Guided Repositioning of FDA-Approved Drugs for PD-L1 Inhibition with In Vitro Anticancer Potential.

ABSTRACT: Programmed death-ligand 1 (PD-L1) is a crucial immune checkpoint protein that tumors often exploit to evade immune surveillance. This study systematically screened a library of 1031 FDA-approved drugs using a high-throughput molecular dynamics approach to identify potential inhibitors targeting PD-L1. From this screening, five promising compounds-vorapaxar, delafloxacin, tenofovir disoproxil, pivmecillinam, and fursultiamine-showed significant binding affinities to PD-L1 and demonstrated cytotoxic activity against A549 lung tumor cells. These candidates were further evaluated through extended molecular dynamics simulations lasting up to 150 ns to assess their structural stability, residue fluctuations, and binding free energy. Among the identified compounds, pivmecillinam demonstrated the

SUBMITTER: Jiang D 

PROVIDER: S-EPMC12110937 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature