S-723595

S-723595 is an oral small molecule G protein-coupled receptor 52 (GPR52) agonist being developed by Shionogi for the treatment of schizophrenia. GPR52 is an orphan GPCR that is highly expressed in the striatum, particularly in the dopamine D2 receptor-expressing medium spiny neurons, as well as in the prefrontal cortex. Activation of GPR52 is hypothesized to modulate both dopaminergic and glutamatergic neurotransmission, potentially providing a multi-faceted approach to treating the positive, negative, and cognitive symptoms of schizophrenia. Unlike traditional antipsychotics that primarily act as D2 receptor antagonists, S-723595 offers a novel mechanism that may improve efficacy while reducing the risk of extrapyramidal side effects and metabolic complications. As of 2024, the compound is in Phase 1 clinical development.