SB-222200

SB-222200 is a potent, selective, orally active and blood-brain barrier (BBB) penetrant NK-3 receptor antagonist. SB-222200 is developed for central nervous system (CNS) disorders^[1]. In Vitro: SB-222200 inhibits ¹²⁵I-[MePhe⁷]neurokinin B (NKB) binding to CHO cell membranes stably expressing the hNK-3 receptor (CHO-hNK-3R) with a K_i of 4.4 nM^[1].
SB-222200 antagonizes NKB-induced Ca²⁺ mobilization in HEK 293 cells stably expressing the hNK-3 receptor (HEK 293-hNK-3R) with an IC₅₀ of 18.4 nM^[1].
SB-222200 is selective for hNK-3 receptors compared with hNK-1 (K_i>100,000 nM) and hNK-2 receptors (K_i=250 nM)^[1].
SB-222200 (10 nM-1 μM) produces a concentration-dependent, surmountable inhibition of NKB-induced Ca²⁺ mobilization in HEK 293-hNK-3R cells^[1].
In Vivo: SB-222200 (5 mg/kg; 30 min pretreatment) produces inhibition of behavioral responses induced by NK-3 receptor-selective agonist senktide (HY-P0187) in mice^[1].
SB-2222006 exhibits moderate oral bioavailability (rat 46%) and C_max (rat 427 ng/mL) following oral administration (rat 10 mg/kg)^[1].
SB-2222006 exhibits terminal elimination half-life (rat 1.9 h) due to high plasma clearance (56 mL/min/kg) following intravenous administration (rat 2.5 mg/kg)^[1].