SK609 HCl (SK609 hydrochloride) is a dopamine D3 receptor (D3R) selective agonist that inhibits norepinephrine transporter proteins and can be used to study Parkinson's disease and cognitive disorders.

Dopamine D3 receptor:1109 nM (EC50)

SK609 activated Gi/o proteins and downstream ERK1/2 signaling, but had no effect on D2R/ERK1/2. The EC50 values of SK609 for [35S]GTPγS binding, ERK1/2 phosphorylation, and β-trap proteins were 1.1±0.2 μM, 50.2±5.9 nM, and 14.4±2.7 μM, respectively; the EC50 value of SK609 at D3R was 1109±273 nM in a competitive inhibition affinity assay [1]. In the competitive inhibition affinity assay of SK609 against D3R, the EC50 value of SK609 at D3R was 1109±273 nM [1].

Safety toxicology studies in rats have shown that the maximum tolerated dose of SK609 is 30 mg/kg, and all doses used in this study were at SK609 [1]; in a PK study in Crab Monkeys, oral administration of SK609 (P.O.; 0.5, 2, and 4 mg/kg) was associated with mean Cmax values at 4.1, 6.4, and 5.0 hours post-dose (Tmax) were 13.7, 69.3, and 218 ng/mL, respectively, with corresponding AUC (0-t) values of 171, 904, and 2938 h.ng/mL; the mean terminal half-life of SK609 in plasma after intravenous administration (2 mg /kg) was 7.9 h. SK609 (i.p.; 2, 4, 6, 8, 10, and 20 mg/kg) was shown to be significant in a rat model of Parkinsonism. Parkinson's model significantly improved and normalized bilateral asymmetry in hemiplegic rats [3].