SB-674042

SB-674042 is a potent and selective non-peptide orexin OX₁ receptor antagonist (K_d=5.03 nM), exhibits 100-fold selectivity for OX₁ over OX₂ receptors with IC₅₀ values of 3.76 nM and 531 nM, respectively^[1][4]. IC50 & Target:Kb: 1.1 nM (OX1 Receptor), 129 nM (OX2 Receptor)^[1]
IC50: 3.76 nM (OX1 Receptor), 531 nM (OX2 Receptor)^[4] In Vitro:SB-674042 ([³H]) (0.2-24 nM; 2 h) shows high-affinity and serves as a radio ligand suitable for labelling human OX1 receptors stably expressed in CHO cells^[1].
SB-674042 (5 μM; 4 ℃ for 30 min, and 37 ℃ for 3 h) reduces the potency of CB1 receptor agonist (HY-14137) to phosphorylate ERK1/2 in HEK293 cells co-expressing the orexin-1 and CB1 receptors^[2].
SB-674042 (1 μM; 24 h) eradicates the increase in mTOR phosphorylation in response to Orexin-A (HY-106224) (1 nM-1 μM; 24 h) in INS-1 cells, indicating activation of the mTOR pathway induced by orexin-A was dependent on the activated OX1 receptor^[3].
In Vivo:SB-674042 (0.3 nM/0.3 μL; icv; single dose) reduces contextual and cues fear freezing responses in Stay animals in Stress Alternatives Model (SMA) in mice^[4].