Project Description

Cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Worldwide, about 1 in 6 deaths, in India 1 in 15 deaths is due to cancer. Despite a significant understanding & substantial improvements, cancer research continues to suffer from extremely low success rates in translating preclinical discoveries into clinical practice. Targeted protein degradation using PROteolysis TArgeting Chimeras (PROTAC), is a new and promising approach in drug discovery for cancer. PROTACs destroy disease-causing proteins by hijacking the natural pathway of ubiquitin proteasome system, rather than inhibiting them like small-molecule inhibitor. Nevertheless, PROTACs have numerous limitations related to poor biodistribution, low stability, and low penetrability in vivo. Most importantly, established small-molecule PROTACs cannot target tumor tissue, thus developing a possibility for off-target effects. This hampers the use of PROTACs in clinical applications. To solve the above problems, herein we propose to link our newly designed PROTACs with a targeting ligand that can deliver the attached PROTACs selectively to cancerous tissue, thereby reducing toxic side effects in the patient and increasing the therapeutic index.