Cytotoxic T-Lymphocyte Associated Protein-4 (Ctla-4) as Potential Drug Target for Cancer Therapeutics

Cytotoxic T-Lymphocyte Associated Protein-4 (Ctla-4) as Potential Drug Target for Cancer Therapeutics Abstract Cancer is the second major cause of death after cardiovascular diseases and is the worldwide threat to the human life. Over 60% of anticancer agents are derived from plants and have a diverse history in the treatment of cancer with significant effects. Present study was performed to investigate the biological action of the natural anticancer compounds having immune stimulating activities and to scrutinize the checkpoint inhibitor from natural sources. Initially 20 plants were screened out having anticancer and immune-stimulatory activities. Dataset of over 100 natural anticancer compounds retrieved from 20 potential plants were subjected to number of filters including ADMET properties, Lipinski rule of five and QSAR to pre-filter irrelevant compounds and screen out potential anticancer candidate that satisfy the drug properties. Using molecular docking approach, five (ascorbic acid, β-carotene, β-sitosterol, kaempferol and mivobulin) shortlisted natural anticancer compounds were docked with cytotoxic T-lymphocyte associated protein-4 (CTLA-4). The current analysis revealed good binding affinity of all compounds to the receptor protein CTLA-4 with high binding score. Among all tested compounds, ascorbic acid was completely buried into the active domain of CTLA-4 and showed strong binding interactions with high score function (- 9.09kcal/mol). We concluded that our identified CTLA-4 inhibitor compound might be used as a potential drug candidate against cancer after thorough evaluation in vitro.