Virtual screening of novel mTOR inhibitors for the potential treatment of human colorectal cancer

In this study, a rational virtual screening strategy has been established and MT-5, a novel mTOR inhibitor with a quinoline scaffold, was obtained from the ChemDiv database. MT-5 showed potent kinase inhibitory activity (IC50: 8.90 μM) and antiproliferative effects against various cancer cell lines, especially HCT-116 cells (IC50: 4.61 μM), and this was 2.2-fold more potent than that of the cisplatin control (IC50: 9.99 μM). Western blot, cell migration, cycle arrest, and apoptosis assays were performed with HCT-116 cells to investigate the potential anticancer mechanism of MT-5. Metabolic stability results in vitro indicated that MT-5 exhibited good stability profiles in artificial gastrointestinal fluids, rat plasma, and liver microsomes. In addition, the key contribution of the residues around the binding pocket of MT-5 in binding to the mTOR protein was also investigated from a computational perspective.PMID:37597440 | DOI:10.1016/j.bioorg.2023.106781
Source: Bioorganic Chemistry - Category: Chemistry Authors: Source Type: research