TIGIT, a protein excessively expressed in cancer patients, interacts with its biological receptors to inactivate tumor-specific NK and T cells. This overexpression is associated with a poor prognosis. Currently, there are no FDA and EMA-approved inhibitors, antibodies, or small molecules targeting TIGIT, with only one small molecule undergoing Phase I clinical trials. A recent release of a database containing compounds active and inactive against TIGIT presents a new opportunity. Our goal is to conduct molecular docking studies using FlexX with these compounds to analyze their interactions with TIGIT’s binding pocket using PoseView. Subsequently, we plan to develop a pharmacophore model based on these compounds/interactions and perform a virtual screening repurposing campaign against recognized databases, such as DrugBank’s approved drugs, to identify new potential inhibitors of TIGIT. The next step will involve generating descriptors to predict the biological activity of these compounds.
Rodrigo intends to achieve the following milestones:
- Completion of molecular docking for the database’s compounds and development of a pharmacophore model.
- Accomplish of Virtual Screening campaign of recognized databases to find potential TIGIT inhibitors.
- After generating descriptors, the identification of promising small molecules that could inhibit TIGIT, followed by preliminary in vitro testing.