Virtual Screening of Small-Molecule Inhibitors Targeting p16INK4a for Cancer Therapy

p16INK4a is a critical tumor suppressor protein involved in regulating cell cycle progression. Mutations or structural changes in p16INK4a have been implicated in various cancers, making it an important therapeutic target. This study utilized computational approaches, including molecular docking and binding site prediction, to identify small-molecule inhibitors capable of binding and stabilizing mutated p16INK4a. We hypothesize that the docked ligands bind strongly to the p16INK4a protein and prevent aggregation. The protein structure was modeled using AlphaFold 3 and analyzed using AutoDock Vina for docking simulations. Based on the favorable binding energies, five potential inhibitors were identified. The pharmaceutical properties of these ligands were computed using the SwissADME web server. Based on this analysis, all the inhibitors demonstrated high gastrointestinal absorption and drug-likeness according to Lipinski’s rule but showed low blood-brain barrier permeability. The current work will be a foundation for designing p16INK4a-targeted therapies to inhibit cancer progression.