PF-592379

PF-592379 is a potent dopamine D₃ receptor agonist with an EC₅₀ of 21 nM. IC50 & Target: EC50: 21 nM (D₃ receptor)^[1][2][3]
Ki: 322 nM (D₃ receptor)^[2]
Ki: 215 nM (hD₃ receptor), 4165 nM (hD₄ receptor)^[3]
EC50: 3.9 μM (hD₄ receptor)^[3] In Vitro: PF-592379 appears to be a full agonist (E_max=95%) when compared with the standard Pramipexole, a D₂/D₃ receptor agonist for the treatment of Parkinson’s disease^[1]. PF-592379 is a potent and selective dopamine 3 agonist with EC₅₀ and K_i of 21 nM and 322 nM, respectively^[2]. In vitro binding assays show that PF-592379 (PF-592,379) selectively binds human D₃ receptors with a high affinity (K_i=215 nM). Although PF-592379 also binds to human D₄ receptors (K_i=4165 nM), it displays a 19-fold binding selectivity for human D₃ over D₄ receptors. PF-592379 fails to bind human D₂ (K_i≥10 μM), D₁ (K_i≥10 μM), or D₅ (K_i≥10 μM) receptors at concentrations of up to 10 µM, and thus is at least 46-fold selective for D₃ over D₂, D₁, and D₅ receptors^[3]. In Vivo: PF-592379 is an oral dopamine 3 agonist in rat, and dog. PF-592379 has low-moderate clearance relative to liver blood flow of 6.3 and 8.5 mL/min/kg in dog and 44.8 and 58.2 mL/min/kg in rat. It has high permeability in Caco-2 cells and is completely absorbed in rat and dog pharmacokinetic studies with an oral bioavailability of 28% in both rats and 61 and 87% in the dogs^[1].