Applying this approach with the goal of discovering potent, novel, and selective inhibitors targeting ALDH3A1 through performing the comprehensive structure-activity relationships optimization resulted in the synthesis of 50 distinct compounds, demonstrating the method's ability to produce potent chemical compounds. Of these, 21 compounds showed activity, indicated by their negative curve class values. Notably, 6 of these active compounds had IC50 values below 30 µM and efficacy values were under -50%, suggesting their strong potency. The most potent compound identified had IC50 of 35 nM, showing the effectiveness of this approach in finding compounds with significant potential for drug discovery. The pharmacophore-based molecular docking was performed using the Molecular Operating Environment (MOE) software . The compound library for docking comprised a diverse set of molecular compounds (approximately 9,000 compounds), each of which was prepared using MOE's ligand preparation tools. This involves energy minimization and the generation of 3D conformations. The crystal structure of human ALDH3A1, PDB ID: 3SZA, was selected as the starting point for our pharmacophore-based molecular docking studies. Initial steps involved cleaning the protein structure, which included the removal of water molecules, irrelevant heteroatoms, and the addition of hydrogens. Protonation states were assigned, followed by energy minimization to optimize the protein's conformation .