I-Corps: Translation Potential of a High Throughput Drug Discovery Platform for Protein Degraders

This I-Corps project focuses on the development of a drug discovery platform to efficiently generate a new class of pharmaceutical drugs. The technology facilitates the generation of expansive drug libraries, enabling unbiased screening of observable characteristics. Importantly, this approach eliminates the need for prior knowledge of protein targets or specific chemicals. Using this platform, researchers can explore the vast landscape of potential drugs with the flexibility to focus on specific cell lines rather than exact protein targets. In addition, the use of this screening process may remove pre-existing bias towards known protein targets that may be treated with current drugs. This platform may lead to the discovery of novel drugs and expand the understanding of their therapeutic potential. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. The solution is based on the development of a high-throughput platform that enables the discovery of heterobifunctional protein degrader drugs. The platform is designed to integrate high-throughput chemistry, direct-to-biology phenotypic cytotoxicity assays, validation in secondary toxicity assays, and rapid confirmation of protein degradation using inactive drug analogs. In addition, the platform is designed to be adaptable and can be implemented into any small-molecule, high-throughput screening platform utilized by institutions involved in drug discovery. The technology may allow researchers to identify degrader drugs, a new class of pharmaceuticals, by focusing on specific cell lines rather than protein targets. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.