Discovery of a selective PI3Kα inhibitor <i>via</i> structure-based virtual screening for targeted colorectal cancer therapy.

ABSTRACT: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, driving an urgent need for effective therapies. A promising avenue of research focuses on the PI3K/AKT/mTOR signalling pathway, which is frequently disrupted by mutations in the PI3Kα subunit. Our cutting-edge study employed a structure-based virtual screening of ∼3000 compounds, leading to the discovery of F0608-0019, a highly potent and selective PI3Kα inhibitor. F0608-0019 demonstrated remarkable efficacy in suppressing HCT116 colorectal cancer cell proliferation, with an IC₅₀ of 12.14 µM, while maintaining high selectivity by minimising activity against other PI3K isoforms. Advanced molecular dynamics simulations highlighted the stability of F0608-0019's binding interactions with key amino

SUBMITTER: Albassam H 

PROVIDER: S-EPMC11852364 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature