Computational Identification of Orantinib as a Potent Small Molecule Targeting Mutant p53 in Non-Small Cell Lung Cancer

This study aimed to identify small molecules targeting mutant p53 using CADD. Five investigational drugs (ABT-751, Antroquinonol, Triapine, Orantinib, Tacedinaline) were analyzed for their binding affinity to the p53 mutant (PDB ID: 4KVP) through molecular docking. Orantinib emerged as the most effective candidate, demonstrating the highest binding affinity (full fitness: -943.96, ΔG: -7.11 kcal/mol) and favorable ADME/toxicity profiles. The study also explored the metabolic pathways disrupted by mutant p53, highlighting its role in glycolysis and oxidative phosphorylation. These findings show the potential of Orantinib as a therapeutic agent for NSCLC and demonstrate the utility of computer-aided drug design (CADD) in targeting mutant p53.