Research Projects

Objective: Design and synthesis of E3 ligase specific PROTAC molecules that target mutant IDH1 proteins. Elucidation of the efficacy of the PROTAC molecules in genome edited cell lines and mouse models. X-ray crystallography analysis of the target protein: PROTAC molecule. The current paradigm of drug discovery follows a simple principle, that a small molecule with appreciable specificity with minimum off-target affects and bioavailability functions as a curative. However, drug resistance arises due to repeated dosage or selective pressure operative in tumor milieu. Thus, in this project molecules that target the protein for degradation have been proposed. Mutant I DH1 are the targets where no PROTAC molecules are available so far. Also, the PROTAC designed and elucidated in this project will be rigorously studied for their efficacy in mouse models and deciphered for their structural mode of binding by x-ray crystallography.