I-Corps: Translation Potential of a Novel Drug Discovery Platform for Targeting G-protein-coupled Receptor Sites

The broader impact/commercial potential of this I-Corps project is based on the development of a platform that enables the discovery of highly specific drugs targeting a unique site on G-protein-coupled receptors (GPCRs). GPCRs are a large family of cell surface receptors that play a crucial role in transmitting signals from the outside to the inside of cells.

These receptors are among the most important drug targets in modern medicine, with many medications, including beta-blockers, antihistamines, and psychiatric drugs, interacting with specific GPCRs. Nearly one-third of all FDA-approved drugs target GPCRs, representing approximately 30% ($890 billion) of the global pharmaceutical market share. GPCRs are desirable drug targets for two main reasons: their druggable sites are easily accessible, and they directly regulate a wide range of physiological and disease processes.

However, conventional GPCR-targeted drugs face limitations in terms of safety and efficacy, restricting the patient populations they can effectively treat. This project proposes a novel drug discovery platform targeting this new GCPR druggable site that could overcome these limitations, enabling the identification of new drug candidates and the development of more effective, safer, and innovative therapies more rapidly.

This I-Corps project utilizes experiential learning coupled with first-hand investigation of the industry ecosystem to assess the translation potential of the proposed technology. It is based on the prior development of a platform technology that enables drug discovery related activities specific to a new molecular mechanism of action targeting G-protein-coupled receptors (GPCRs) as a new druggable site.

Compared to other druggable sites on GPCRs, this site is highly specific in terms of its composition among the 800+ different receptor isoforms. The technology that was developed in the process of characterizing this new site is a platform that enables identification of compounds that target this site. A key component of this platform is a patented high-throughput screening assay that detects nuanced differences in GPCR drug effectiveness that are not detectable using other high-throughput screening formats.

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.