SB-334867 | CAS#792173-99-0 | Orexin Antagonist

MedKoo Cat#: 530968 | Name: SB-334867 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SB-334867 is an orexin antagonist. It 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.

Chemical Structure

SB-334867 free base

CAS#792173-99-0 (free base)

Theoretical Analysis

MedKoo Cat#: 530968

Name: SB-334867 free base

CAS#: 792173-99-0 (free base)

Chemical Formula: C17H13N5O2

Exact Mass: 319.1069

Molecular Weight: 319.32

Elemental Analysis: C, 63.94; H, 4.10; N, 21.93; O, 10.02

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to Ship
25mg	USD 190.00	Ready to ship
50mg	USD 350.00	Ready to ship
100mg	USD 550.00	Ready to ship
200mg	USD 950.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 3,250.00	Ready to ship
2g	USD 5,850.00	Ready to ship

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Related CAS #

792173-99-0 (free base) 249889-64-3 (HCl)

Synonym

SB-334867; SB 334867; SB334867.

IUPAC/Chemical Name

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

InChi Key

AKMNUCBQGHFICM-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

O=C(NC1=CC=NC2=CC=CN=C12)NC3=CC=C4N=C(C)OC4=C3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T06K23

View CoA: current batch, Lot#A8T08K11

QC Data

View QC data: current batch, Lot#A8T06K23

View QC data: current batch, Lot#A8T08K11

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SB-334867 free base is an OX1 receptor antagonist that shows selectivity over OX2 (pKb=7.4), 100-fold over 5-HT2B, 5-HT2C with pKi values of 5.4 and 5.3, respectively. SB-334867 reduces ethanol consumption and inhibits the acquisition of morphine-induced sensitization to locomotor activity in vivo.

In vitro activity:

SB-334867 acts as a non-peptide antagonist specific to the OX1 receptor. SB-334867 inhibited orexin-A and orexin-B-induced calcium responses, but had no effect on the UTP-induced calcium response in CHO-OX1 cells. SB-334867 also inhibited OX2 mediated calcium responses. SB-334867 was devoid of agonist properties in either cell-line. Reference: Br J Pharmacol. 2001 Mar;132(6):1179-82. https://pubmed.ncbi.nlm.nih.gov/11250867/

In vivo activity:

SB-334867 inhibited the acquisition of morphine-induced sensitization to locomotor activity in mice. SB-334867 treatment caused significant alterations in the mRNA expression of orexin, dopamine, and adenosine receptors in multiple brain structures. Additionally, there were changes in the expression of markers associated with glial cells (GFAP and Iba-1). Reference: Mol Neurobiol. 2018 Nov;55(11):8473-8485. https://pubmed.ncbi.nlm.nih.gov/29557083/

	Solvent	mg/mL	mM
Solubility
	DMSO	48.3	151.29
	0.1M HCl	6.0	18.79
	Ethanol	4.1	12.84

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 319.32 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wen J, Zhao Y, Shen Y, Guo L. Effect of orexin A on apoptosis in BGC-823 gastric cancer cells via OX1R through the AKT signaling pathway. Mol Med Rep. 2015 May;11(5):3439-44. doi: 10.3892/mmr.2015.3190. Epub 2015 Jan 13. PMID: 25586545. 2. Smart D, Sabido-David C, Brough SJ, Jewitt F, Johns A, Porter RA, Jerman JC. SB-334867-A: the first selective orexin-1 receptor antagonist. Br J Pharmacol. 2001 Mar;132(6):1179-82. doi: 10.1038/sj.bjp.0703953. PMID: 11250867; PMCID: PMC1572677. 3. Stanquini LA, Sartim AG, Joca SRL. Orexin A injection into the ventral medial prefrontal cortex induces antidepressant-like effects: Possible involvement of local Orexin-1 and Trk receptors. Behav Brain Res. 2020 Oct 1;395:112866. doi: 10.1016/j.bbr.2020.112866. Epub 2020 Aug 19. PMID: 32827568. 4. Łupina M, Tarnowski M, Baranowska-Bosiacka I, Talarek S, Listos P, Kotlińska J, Gutowska I, Listos J. SB-334867 (an Orexin-1 Receptor Antagonist) Effects on Morphine-Induced Sensitization in Mice-a View on Receptor Mechanisms. Mol Neurobiol. 2018 Nov;55(11):8473-8485. doi: 10.1007/s12035-018-0993-0. Epub 2018 Mar 20. PMID: 29557083; PMCID: PMC6153720.

In vitro protocol:

In vivo protocol:

1. Stanquini LA, Sartim AG, Joca SRL. Orexin A injection into the ventral medial prefrontal cortex induces antidepressant-like effects: Possible involvement of local Orexin-1 and Trk receptors. Behav Brain Res. 2020 Oct 1;395:112866. doi: 10.1016/j.bbr.2020.112866. Epub 2020 Aug 19. PMID: 32827568. 2. Łupina M, Tarnowski M, Baranowska-Bosiacka I, Talarek S, Listos P, Kotlińska J, Gutowska I, Listos J. SB-334867 (an Orexin-1 Receptor Antagonist) Effects on Morphine-Induced Sensitization in Mice-a View on Receptor Mechanisms. Mol Neurobiol. 2018 Nov;55(11):8473-8485. doi: 10.1007/s12035-018-0993-0. Epub 2018 Mar 20. PMID: 29557083; PMCID: PMC6153720.

1: Haynes AC, Jackson B, Chapman H, Tadayyon M, Johns A, Porter RA, Arch JR. A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regul Pept. 2000 Dec 22;96(1-2):45-51. doi: 10.1016/s0167-0115(00)00199-3. PMID: 11102651. 2: Duxon MS, Stretton J, Starr K, Jones DN, Holland V, Riley G, Jerman J, Brough S, Smart D, Johns A, Chan W, Porter RA, Upton N. Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement. Psychopharmacology (Berl). 2001 Jan 1;153(2):203-9. doi: 10.1007/s002130000550. PMID: 11205420. 3: Jones DN, Gartlon J, Parker F, Taylor SG, Routledge C, Hemmati P, Munton RP, Ashmeade TE, Hatcher JP, Johns A, Porter RA, Hagan JJ, Hunter AJ, Upton N. Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity. Psychopharmacology (Berl). 2001 Jan 1;153(2):210-8. doi: 10.1007/s002130000551. PMID: 11205421. 4: Smart D, Sabido-David C, Brough SJ, Jewitt F, Johns A, Porter RA, Jerman JC. SB-334867-A: the first selective orexin-1 receptor antagonist. Br J Pharmacol. 2001 Mar;132(6):1179-82. doi: 10.1038/sj.bjp.0703953. PMID: 11250867; PMCID: PMC1572677. 5: Rodgers RJ, Halford JC, Nunes de Souza RL, Canto de Souza AL, Piper DC, Arch JR, Upton N, Porter RA, Johns A, Blundell JE. 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. doi: 10.1046/j.0953-816x.2001.01518.x. PMID: 11298806. 6: Bingham S, Davey PT, Babbs AJ, Irving EA, Sammons MJ, Wyles M, Jeffrey P, Cutler L, Riba I, Johns A, Porter RA, Upton N, Hunter AJ, Parsons AA. Orexin-A, an hypothalamic peptide with analgesic properties. Pain. 2001 May;92(1-2):81-90. doi: 10.1016/s0304-3959(00)00470-x. PMID: 11323129. 7: Porter RA, Chan WN, Coulton S, Johns A, Hadley MS, Widdowson K, Jerman JC, Brough SJ, Coldwell M, Smart D, Jewitt F, Jeffrey P, Austin N. 1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor. Bioorg Med Chem Lett. 2001 Jul 23;11(14):1907-10. doi: 10.1016/s0960-894x(01)00343-2. PMID: 11459658. 8: Soffin EM, Evans ML, Gill CH, Harries MH, Benham CD, Davies CH. SB-334867-A antagonises orexin mediated excitation in the locus coeruleus. Neuropharmacology. 2002 Jan;42(1):127-33. doi: 10.1016/s0028-3908(01)00156-3. PMID: 11750922. 9: Haynes AC, Chapman H, Taylor C, Moore GB, Cawthorne MA, Tadayyon M, Clapham JC, Arch JR. Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice. Regul Pept. 2002 Mar 15;104(1-3):153-9. doi: 10.1016/s0167-0115(01)00358-5. PMID: 11830290. 10: Yamamoto T, Nozaki-Taguchi N, Chiba T. Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test. Br J Pharmacol. 2002 Sep;137(2):170-6. doi: 10.1038/sj.bjp.0704851. PMID: 12208773; PMCID: PMC1573477. 11: Matsuo K, Kaibara M, Uezono Y, Hayashi H, Taniyama K, Nakane Y. Involvement of cholinergic neurons in orexin-induced contraction of guinea pig ileum. Eur J Pharmacol. 2002 Sep 27;452(1):105-9. doi: 10.1016/s0014-2999(02)02300-2. PMID: 12323391. 12: Rodgers RJ, Ishii Y, Halford JC, Blundell JE. Orexins and appetite regulation. Neuropeptides. 2002 Oct;36(5):303-25. doi: 10.1016/s0143-4179(02)00085-9. PMID: 12450737. 13: Hirota K, Kushikata T, Kudo M, Ohkawa H, Kudo T, Lambert DG, Smart D, Matsuki A. Lack of an interaction between orexinergic and opioid/nociceptinergic systems in rat cerebrocortical slices. Neurosci Lett. 2003 Apr 17;340(3):173-6. doi: 10.1016/s0304-3940(03)00099-5. PMID: 12672534. 14: Smith MI, Piper DC, Duxon MS, Upton N. Evidence implicating a role for orexin-1 receptor modulation of paradoxical sleep in the rat. Neurosci Lett. 2003 May 8;341(3):256-8. doi: 10.1016/s0304-3940(03)00066-1. PMID: 12697296. 15: Ehrström M, Näslund E, Ma J, Kirchgessner AL, Hellström PM. Physiological regulation and NO-dependent inhibition of migrating myoelectric complex in the rat small bowel by OXA. Am J Physiol Gastrointest Liver Physiol. 2003 Oct;285(4):G688-95. doi: 10.1152/ajpgi.00061.2003. Epub 2003 Jun 19. PMID: 12816759. 16: Hirota K, Kushikata T, Kudo M, Kudo T, Smart D, Matsuki A. Effects of central hypocretin-1 administration on hemodynamic responses in young-adult and middle-aged rats. Brain Res. 2003 Aug 15;981(1-2):143-50. doi: 10.1016/s0006-8993(03)03002-6. PMID: 12885435. 17: Cheng JK, Chou RC, Hwang LL, Chiou LC. Antiallodynic effects of intrathecal orexins in a rat model of postoperative pain. J Pharmacol Exp Ther. 2003 Dec;307(3):1065-71. doi: 10.1124/jpet.103.056663. Epub 2003 Oct 9. PMID: 14551290. 18: Kushikata T, Hirota K, Yoshida H, Kudo M, Lambert DG, Smart D, Jerman JC, Matsuki A. Orexinergic neurons and barbiturate anesthesia. Neuroscience. 2003;121(4):855-63. doi: 10.1016/s0306-4522(03)00554-2. PMID: 14580935. 19: Bernard R, Lydic R, Baghdoyan HA. Hypocretin-1 causes G protein activation and increases ACh release in rat pons. Eur J Neurosci. 2003 Oct;18(7):1775-85. doi: 10.1046/j.1460-9568.2003.02905.x. PMID: 14622212. 20: Wu X, Gao J, Yan J, Owyang C, Li Y. Hypothalamus-brain stem circuitry responsible for vagal efferent signaling to the pancreas evoked by hypoglycemia in rat. J Neurophysiol. 2004 Apr;91(4):1734-47. doi: 10.1152/jn.00791.2003. Epub 2003 Nov 26. Retraction in: J Neurophysiol. 2022 Dec 1;128(6):1506. doi: 10.1152/jn.00791.2003_RET. PMID: 14645380.