G protein-coupled receptors (GPCRs) are key targets for pharmaceuticals, yet no approved drugs exist for adhesion G protein-coupled receptors (aGPCRs), which form a large family within the GPCR group. This is due to their unusal activation mechanism involving autoproteolytic cleavage, subsequent formation of a dimeric receptor complex comprised of N-terminal (NTF) and C-terminal (CTF) fragments, and mechanical stimulation. To meet the need for aGPCR drugs, we developed the NTF Release Sensor (NRS), a molecular reporter that senses NTF-CTF separation.
We aim to adapt this technology for high-throughput screening (HTS) to identify therapeutic compounds for aGPCRs. A crucial step is the generation of transgenic cell lines expressing aGPCR-NRS, ensuring stable long-term gene expression and reproducibility of screening results.
