Blocking the Immunosuppressive Effect of the TIM3/GAL9 Signaling Pathway by TIM3 Inhibition
T cells are the most important tools of the adaptive anti-tumor immune response. In various cancer types, the TIM3/Galectin-9 signaling pathway has been shown to suppress the anti-tumor immune response by restricting T cell function. In our project, we aimed to develop a drug that prevents TIM3/Gal9 binding by inhibiting the TIM3 protein, which is highly expressed by CD8+ and CD4+ T cells in the tumor microenvironment. After accessing the 3D structure of the TIM3 protein, we made the protein ready for docking and prepared the chemical library required for Virtual Screening and performed virtual drug screening with the PyRx Virtual Screening tool. Ledipasvir (GS5885), Conivaptan Hydrochloride and Imatinib Mesylate were evaluated as TIM3 inhibitors in the data we obtained as a result of virtual drug screening. Then, docking procedures of the 3 molecules were performed and binding conformations were obtained. As a result of the studies, it was proved that Ledipasvir, Conivaptan Hydrochloride and Imatinib Mesylate ligands with ∆G° values less than -9 in the virtual drug screen can be evaluated as inhibitors for TIM3 protein under in-silico conditions. The toxicity and physicochemical properties of the three identified molecules were then analyzed and it was found that among the Ledipasvir, Conivaptan Hydrochloride and Imatinib Mesylate molecules, Imatinib Mesylate had the least toxicity and the most suitable physicochemical properties for treatment.