SB-674042

SB-674042 is a potent and selective non-peptide orexin OX1 receptor antagonist (Kd = 3.76 nM); exhibits 100-fold selectivity for OX1 over OX2 receptors.IC50 value: 3.76 nM (Kd)Target: OX1 receptorSB-674042 has no effect at serotonergic, dopaminergic, adrenergic or purinergic receptors. Inhibits orexin 1-induced Ca2+ mobilization in CHO-DG44 cells stably transfected with the OX1 receptor.

References:
[1]. Heifetz, Alexander; Morris, G. Benjamin; Biggin, Philip C. et al. Study of Human Orexin-1 and -2 G-Protein-Coupled Receptors with Novel and Published Antagonists by Modeling, Molecular Dynamics Simulations, and Site-Directed Mutagenesis. Biochemistry (2012), 51(15), 3178-3197.
[2]. Malherbe, Pari; Roche, Olivier; Marcuz, Anne et al. Mapping the binding pocket of dual antagonist Almorexant to human orexin 1 and orexin 2 receptors: comparison with the selective OX1 antagonist SB-674042 and the selective OX2 antagonist N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl-acetamide (EMPA). Molecular Pharmacology (2010), 78(1), 81-93.
[3]. Malherbe, Pari; Borroni, Edilio; Pinard, Emmanuel et al. Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists. Molecular Pharmacology (2009), 76(3), 618-631.
[4]. Ellis, James; Pediani, John D.; Canals, Meritxell et al. Orexin-1 Receptor-Cannabinoid CB1 Receptor Heterodimerization Results in Both Ligand-dependent and -independent Coordinated Alterations of Receptor Localization and Function. Journal of Biological Chemistry (2006), 281(50), 38812-38824.
[5]. Langmead, Christopher J.; Jerman, Jeffrey C.; Brough, Stephen J. et al. Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. British Journal of Pharmacology (2004), 141(2), 340-346.