SB-334867, an orexin antagonist

SB-334867 is an orexin antagonist. SB-334867 was the first non-peptide antagonist developed that is selective for the orexin receptor subtype OX1, with around 50x selectivity for OX1 over OX2 receptors. It has been shown to produce sedative and anorectic effects in animals, and has been useful in characterising the orexinergic regulation of brain systems involved with appetite and sleep, as well as other physiological processes. Orexin antagonists have multiple potential clinical applications including the treatment of drug addiction, insomnia, obesity and diabetes.

Product information

CAS Number: 792173-99-0

Molecular Weight: 319.32

Formula: C17H13N5O2

Synonym:

SB-334867

SB 334867

SB334867

Related CAS Number:

249889-64-3 (SB-334867 HCl)

Chemical Name: N-(2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl-urea

Smiles: CC1=NC2=CC=C(C=C2O1)NC(=O)NC1=CC=NC2=CC=CN=C12

InChiKey: AKMNUCBQGHFICM-UHFFFAOYSA-N

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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Solubility (25°C) DMSO: 63 mg/mL(197.29 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

SB-334867 (100 pM– 10 μM) inhibits the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses in a concentration-dependent manner, with apparent pKb values of 7.27±0.04 and 7.23±0.03, but has no effect on the calcium response elicited by UTP (3 μM), which activates an endogenous purinergic receptor in CHO-OX1 and CHO-OX2 cells.

In Vivo:

SB-334867 (intraperitoneal injection; 20 mg/kg; 20 days) administers 15 min before morphine injection can significantly decrease the effect of the morphine challenge dose in mice in comparison with the sporadically morphine-treated group. SB-334867 (intraperitoneal injection; 3, 10 and 30 mg/kg) significantly reduces ethanol intake relative to vehicle and does not effect water consumption in female P rats. SB-334867 (intraperitoneal injection; 3, 10 and 30 mg/kg) reduces ethanol consumption at the 30 mg/kg dose, high dose suppresses sucrose intake relative to vehicle, and it results in lower blood ethanol concentrations (BECs) relative to both the 10 and 30 mg/kg doses.

References:

1. Hooshmand B, Azizi H, Javan M, Semnanian S. Intra-LC microinjection of orexin type-1 receptor antagonist SB-334867 attenuates the expression of glutamate-induced opiate withdrawal like signs during the active phase in rats. Neurosci Lett. 2017 Jan 1;636:276-281. doi: 10.1016/j.neulet.2016.10.051. Epub 2016 Nov 2. PubMed PMID: 27816550.
2. Kordi Jaz E, Moghimi A, Fereidoni M, Asadi S, Shamsizadeh A, Roohbakhsh A. SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats. Fundam Clin Pharmacol. 2017 Apr;31(2):201-207. doi: 10.1111/fcp.12249. Epub 2016 Nov 23. PubMed PMID: 27739093.
3. Mayannavar S, Rashmi KS, Rao YD, Yadav S, Ganaraja B. Effect of Orexin A antagonist (SB-334867) infusion into the nucleus accumbens on consummatory behavior and alcohol preference in Wistar rats. Indian J Pharmacol. 2016 Jan-Feb;48(1):53-8. doi: 10.4103/0253-7613.174528. PubMed PMID: 26997723; PubMed Central PMCID: PMC4778208.
4. Socała K, Szuster-Ciesielska A, Wlaź P. SB 334867, a selective orexin receptor type 1 antagonist, elevates seizure threshold in mice. Life Sci. 2016 Apr 1;150:81-8. doi: 10.1016/j.lfs.2016.02.075. Epub 2016 Feb 23. PubMed PMID: 26916826.
5. Vanderhaven MW, Corn...

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