In Silico Discovery of a Novel Natural Product Targeting PI3Kα for the Treatment of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) remains a major health burden, with abnormal activation of phosphatidylinositol 3-kinase alpha (PI3Kα) strongly implicated in its pathogenesis. Targeting PI3Kα represents a promising therapeutic strategy. In this study, we employed structure-based virtual screening to identify natural small-molecule inhibitors of PI3Kα. A total of 12,800 molecules were screened, and five compounds were selected for further evaluation based on binding affinity and interaction patterns. Pharmacokinetic properties were assessed using ADMET predictions, and molecular dynamics (MD) simulations were conducted to validate the binding stability. Among the candidates, Apigetrin demonstrated favorable ADMET properties, a high safety profile, and stable binding within the ATP-binding pocket of PI3Kα. These findings suggest that Apigetrin is a promising natural PI3Kα inhibitor with potential therapeutic relevance for HNSCC.