FMJ-01-054 is a selective dopamine D4 receptor (D4R) antagonist with a Ki value of 77.7 nM. It exhibits subtype selectivity for D2R and D3R. FMJ-01-054 inhibits D4R-mediated β-arrestin recruitment and cAMP production, with IC50 values of 3800 nM and 134 nM, respectively. In rats, it demonstrates an ideal plasma half-life and brain exposure. FMJ-01-054 is applicable in neuropsychiatric disorder research.

D4 receptor (human):77.7 nM (Ki)

FMJ-01-054 (compound 17) demonstrates high affinity binding to human dopamine D4 receptors (K i = 77.7 nM) with a selectivity for D4 over D2 and D3 receptors greater than 1287-fold. It acts as an antagonist at dopamine D4 receptors with an IC50 of 3800 nM, displaying no agonistic activity. As an antagonist, FMJ-01-054 (30 min) inhibits dopamine D4 receptor-mediated cAMP production with an IC50 of 134 nM. Furthermore, it exhibits metabolic stability in rat and human liver microsomes, with half-lives of 64.77 min and 46.84 min, respectively.

FMJ-01-054 (compound 17) administered at 5 mg/kg via intraperitoneal injection as a single dose demonstrates favorable in vivo pharmacokinetic properties in Sprague−Dawley rats, with a plasma half-life of 2.10 hours, a brain Cmax of 3.04 nmol/g, and a brain-to-blood ratio of 0.30.