PW0787

PW0787 is a potent, selective, orally active, and brain-penetrant GPR52 agonist (EC50=135 nM). PW0787 suppresses psychostimulant behavior[1].

Signaling Pathways >> Others >> Others

Research Areas >> Neurological Disease

EC50: 135 nM (GPR52)[1]

PW0787 (0.3, 1, 3, or 10 mg/kg; IP) displays antipsychotic-like activity by significantly inhibiting amphetamine-induced hyperlocomotor behavior in mice[1]. PW0787 is evaluated in rats after a single dose of 20 mg/kg by oral (PO) or 10 mg/kg by intravenous (IV) administration. PW0787 has excellent plasma exposure after PO (AUC0-inf = 13,749 ng•h/mL) and IV dosing (AUC0-inf=9030 ng•h/mL), as well as high maximum serum concentration following PO (Cmax=3407 ng/mL) and IV administration (Cmax=6726 ng/mL). Additionally, PW0787 displays good volume of plasma distribution (Vss=1.5 L/kg) and acceptable plasma clearance (CL=1.1 L/h/kg) after 10 mg/kg IV. Excellent oral bioavailability (F) with the value of 76% is observed[1]. Animal Model: Naïve male C57/BL6 mice weighing between 24 and 31 g Dosage: 0.3, 1, 3, or 10 mg/kg (dissolved in 0.9% saline containing 20% HP-β-CD with a final pH of the solution adjusted to 7.4) Administration: IP Result: Suppressed amphetamine (AMPH)-induced horizontal activity at both 3 mg/kg and 10 mg/kg doses.

[1]. Wang P, et al. Discovery of Potent and Brain-Penetrant GPR52 Agonist that Suppresses Psychostimulant Behavior. J Med Chem. 2020;63(22):13951-13972.