PW0866

PW0866 (also known as compound 24f) is a potent, selective, and G protein-biased agonist of the orphan G protein-coupled receptor 52 (GPR52). Developed by researchers at the University of Texas Medical Branch (UTMB), PW0866 selectively activates Gs/Golf-mediated cAMP signaling with minimal recruitment of β-arrestin, which significantly reduces receptor desensitization compared to balanced agonists. GPR52 is highly expressed in the striatum and co-expressed with dopamine D2 receptors in medium spiny neurons. By activating cAMP signaling, GPR52 agonists functionally oppose D2 receptor signaling, making GPR52 a promising therapeutic target for neuropsychiatric and neurological disorders such as schizophrenia, psychosis, and substance use disorders. Preclinical studies of PW0866 have demonstrated improved potency and efficacy, though its brain exposure is limited, suggesting a need for further optimization.

Other names

24fcompound 24fcompound24fcompound-24f