GPR17 – orphan G protein-coupled receptor with therapeutic potential

The orphan G protein-coupled receptor (GPCR) GPR17, whose physiological agonist remains unknown, has emerged as a promising drug target for multiple sclerosis (MS). Blockade of the receptor enables remyelination and may offer a novel therapeutic strategy for MS. Only recently, potent and selective tool compounds for GPR17 have become available, and patents on antagonists have surged, leading to the first clinical candidate, the GPR17 antagonist PTD802, which is to be developed for MS therapy. This may pave the way for further clinical studies exploring additional indications, such as neurodegenerative diseases. The newly determined cryo-electron microscopy (cryo-EM) structure of GPR17 is expected to facilitate future structure-based drug design efforts. This review presents and discusses these latest developments, providing a timely and comprehensive overview to guide future research in the field.