Myeloid Cell Leukemia-1 (Mcl-1) Protein’s Inhibition Activity Against Cancer

Abstract

Objective: To evaluate potential MCL-1 inhibitors with improved efficacy, minimal side effects and reduced resistance for targeted cancer therapy.

Methods: In silico molecular docking was executed, using Autodock vina between active site residues of Mcl-1 protein and eight screened ligands (Screened using Swiss ADME and ProTox 3.0 server) with the least toxicity, including no carcinogenicity, mutagenicity, Lipinski rules violation. 

Results: Visual inspection and binding energy analysis of eight sequentially screened drugs (trazodone hydrochloride, tetrahydrozoline hydrochloride, ketotifen, pentazocine, quinine dihydrochloride, galantamine hydrobromide, ivabradine and metoprolol) demonstrate significant binding affinities and efficient interactions with active site amino acid residue of MCL-1 protein, suggesting their possibility as an effective anti-tumor agent.

Conclusion: This advanced computational screening predicts these eight drugs as potential MCL-1 inhibitors due to their interaction with the active site binding amino acids, mainly (His224A, Thr266A, Leu267A, Met231A, Val253A, and Phe270A), in facilitating strong drug binding through a novel mechanism of action, potentially destabilizing MCL-1, and inhibiting its function. Overall, our findings suggest these drugs could be a promising therapeutic strategy for tumors, though additional experimentation is necessary to validate these results.