This project aims to apply a mammalian small molecule protein interaction trap (MASPIT) to discover new intracellular therapeutic targets. In MASPIT a dihydrofolate reductase fusion protein is used to anchor the methotrexate (MTX) part of a MTX-bait conjugate, which permits to present the bait to the intracellular environment. A bait-prey interaction activates the JAK2-STAT3 signalization and can be easily detected via a reporter protein (e.g., luciferase), whose expression is controlled by a STAT3-responsive promoter.The goal of this project is to devise a suitable strategy for the synthesis of MTX-bait conjugates to identify hitherto unknown targets of therapeutically interesting small molecules.