SB-674042 is a potent, selective dual antagonist of the non-peptide orexigenic peptides OX1 and OX2 receptors, with IC50 values of 3.76 nM and 531 nM, respectively. SB-674042 is suitable for the treatment of depression.

OX2 receptor:531 nM, OX2 receptor:129 nM (Ki), OX1 receptor:1.1 nM (Ki), OX1 receptor:3.76 nM

[(3)H]SB-674042 is a specific, high-affinity radioligand for the OX(1) receptor. Specific binding of [(3)H]SB-674042 was saturable in both whole cell and membrane formats. Analyses suggested a single high-affinity site, with K(d) values of 3.76+/-0.45 and 5.03+/-0.31 nM[1]。Treatment of cells co-expressing the orexin-1 and CB1 receptors with the orexin-1 receptor antagonist SB-674042 also resulted in re-localization of both receptors to the cell surface. Treatment with SB-674042 also reduced the potency of a CB1 receptor agonist to phosphorylate ERK1/2 only when the two receptors were co-expressed[4].

In the Stress Alternatives Model (SMA) in mice, administration of SB-674042 at a dose of 0.3 nM/0.3 μL via icv (intracerebroventricular injection) reduces contextual and cue fear freezing responses in Stay animals[2].