Potent FOXO3a Activators from Biologically Active Compound Library for Cancer Therapeutics: An in silico Approach.

The forkhead transcription factor FOXO3a is a member of the FOXO subfamily, which controls a number of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage, and carcinogenesis. In addition, it reacts to a number of biological stressors such as oxidative stress and UV radiation. FOXO3a has been predominantly associated with many diseases including cancer. Recent research suggests that FOXO3a suppresses tumor growth in cancer. By cytoplasmic sequestration of the FOXO3a protein or mutation of the FOXO3a gene, FOXO3a is commonly rendered inactive in cancer cells. Furthermore, the onset and development of cancer are linked to its inactivation. In order to reduce and prevent tumorigenesis, FOXO3a needs to be activated. So, it is critical to develop new strategies to enhance FOXO3a expression for cancer therapy. Hence, the present study has been aimed to screen small molecules targeting FOXO3a using bioinformatics tools. Molecular docking and molecular dynamic simulation studies reveal the potent FOXO3a activating small molecules such as F3385-2463, F0856-0033, and F3139-0724. These top three compounds will be subjected to further wet experiments. The findings of this study will lead us to explore the potent FOXO3a activating small molecules for cancer therapeutics.