SB-334867 free base

• CAT Number: I004895
• CAS Number: 792173-99-0
• Molecular Formula: C17H13N5O2
• Molecular Weight: 319.324
• Purity: ≥95%
• Synonyms: 1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea
• Target: OX Receptor
• Solubility: DMSO : ≥ 49 mg/mL
• Storage: Store at -20C
• IC50: 7.2 (pKb) [1]
• InChI: InChI=1S/C17H13N5O2/c1-10-20-12-5-4-11(9-15(12)24-10)21-17(23)22-14-6-8-18-13-3-2-7-19-16(13)14/h2-9H,1H3,(H2,18,21,22,23)
• InChIKey: AKMNUCBQGHFICM-UHFFFAOYSA-N
• SMILES: CC1=NC2=C(O1)C=C(C=C2)NC(=O)NC3=C4C(=NC=C3)C=CC=N4

SB-334867 free base is a selective non-peptide orexin OX1 receptor antagonist with a pKb value of 7.2.IC50 value: 7.2 (pKb) [1]Target: orexin OX1 receptorin vitro: SB-334867-A inhibited the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses (pK(B)=7.27+/-0.04 and 7.23+/-0.03 respectively, n=8), but had no effect on the UTP (3 microM)-induced calcium response in CHO-OX(1) cells. SB-334867-A (10 microM) also inhibited OX(2) mediated calcium responses (32.7+/-1.9% versus orexin-A) [1].in vivo: Single-unit recordings in anesthetized rats demonstrated the central effects of the selective orexin-1 receptor antagonist SB-334867 (2 mg/kg, intravenous), as it reversed the excitatory effects of orexin-A administration (6 microg, intracerebroventricular) on the activity of locus coeruleus (LC) cells [2]. The ICV injection of SB-334867 alone had no effect on the formalin-induced nociceptive behaviors. Pre-treatment with SB-334867 at a dose of 0.5 nmol significantly attenuated the analgesia induced by morphine (at dose 1.5mg/kg of morphine; interphase and phase 2B and at dose 3mg/kg of morphine just phase 2B of formalin test) [3]. Administered alone, SB-334867 (30 mg/kg, but not lower doses) significantly reduced food intake and most active behaviours (eating, grooming, sniffing, locomotion and rearing), while increasing resting. Pretreatment with SB-334867 dose-dependently blocked these effects of orexin-A, with significant antagonism evident at dose levels (3-10 mg/kg) below those required to produce intrinsic behavioural effects under present test conditions in rats [4].Toxicity: Acute systemic treatment with the selective orexin-1 (OX1R) antagonist SB-334867 reduces food intake in rats, an effect associated with an acceleration in behavioural satiety and unrelated to gross behavioural disruption, alterations in palatability, or toxicity.

Reference

[1]. Smart D, et al. SB-334867-A: the first selective orexin-1 receptor antagonist. Br J Pharmacol. 2001 Mar;132(6):1179-82.
[2]. Rasmussen K, et al. The orexin-1 receptor antagonist SB-334867 blocks the effects of antipsychotics on the activity of A9 and A10 dopamine neurons: implications for antipsychotic therapy. Neuropsychopharmacology. 2007 Apr;32(4):786-92.
[3]. Azhdari-Zarmehri H, et al. Orexin receptor type-1 antagonist SB-334867 decreases morphine-induced antinociceptive effect in formalin test. Pharmacol Biochem Behav. 2013 Nov;112:64-70.
[4]. Rodgers RJ, et al. SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats. Eur J Neurosci. 2001 Apr;13(7):1444-52.