Molecular docking study demonstrates potent Bcl-2 binding affinity by withdrawn drugs, indicating potential candidates for repurposed cancer therapies.
Key Points
To evaluate the Bcl-2 inhibitory potential of clinically withdrawn pharmaceuticals using computational docking to discover viable candidates for anticancer repurposing.
Retrieved chemical profiles of clinically withdrawn drugs from the DrugBank database.
Performed molecular docking simulations against the Bcl-2 target pocket using MzDOCK software, with venetoclax serving as the reference standard.
Evaluated key binding interactions, including hydrogen bonds, hydrophobic contacts, and salt bridges, for top-affinity candidates.
Plicamycin exhibited the highest binding affinity at -11.5 kJ/mol, outperforming the clinical reference venetoclax at -10.3 kJ/mol.
Plicamycin interacted with key residues shared with venetoclax while establishing additional stabilizing contacts within the Bcl-2 binding pocket.
Depreotide, piperacetazine, and phenolphthalein also showed favorable binding profiles against Bcl-2.