SB-408124 | CAS#288150-92-5 | OX1 receptor antagonist

MedKoo Cat#: 526763 | Name: SB-408124

Description:

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

SB-408124 is an elective non-peptide orexin OX1 receptor antagonist (Kb values are 21.7 and 1405 nM for human OX1 and OX2 receptors respectively). A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states.

Chemical Structure

SB-408124

CAS#288150-92-5 (free base)

Theoretical Analysis

MedKoo Cat#: 526763

Name: SB-408124

CAS#: 288150-92-5 (free base)

Chemical Formula: C19H18F2N4O

Exact Mass: 356.1449

Molecular Weight: 356.38

Elemental Analysis: C, 64.04; H, 5.09; F, 10.66; N, 15.72; O, 4.49

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 weeks
100mg	USD 750.00	2 Weeks
1g	USD 4,250.00	2 Weeks

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Related CAS #

288150-92-5 (free base) 1431697-90-3 (HCl)

Synonym

SB-408124; SB 408124; SB408124 free base

IUPAC/Chemical Name

N-(6,8-Difluoro-2-methyl-4-quinolinyl)-N'-[4-(dimethylamino)phenyl]urea

InChi Key

JTARFZSNUAGHRB-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H18F2N4O/c1-11-8-17(15-9-12(20)10-16(21)18(15)22-11)24-19(26)23-13-4-6-14(7-5-13)25(2)3/h4-10H,1-3H3,(H2,22,23,24,26)

SMILES Code

O=C(NC1=CC=C(N(C)C)C=C1)NC2=CC(C)=NC3=C(F)C=C(F)C=C23

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

Related CAS# 288150-92-5 (free base); 1431697-90-3 (HCl).

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SB-408124 is a elective non-peptide orexin OX1 receptor antagonist (Kb values are 21.7 and 1405 nM for human OX1 and OX2 receptors, respectively).

In vitro activity:

Orexin peptides demonstrated low affinity for the OX(1) receptor, with SB-408124, SB-334867, and SB-410220 showing high affinity and functional antagonism towards the OX(1) receptor. These antagonists also displayed selectivity over the orexin-2 receptor, indicating their potential as tools to explore OX(1) receptor functions. Reference: Br J Pharmacol. 2004 Jan;141(2):340-6. https://pubmed.ncbi.nlm.nih.gov/14691055/

In vivo activity:

SB-408124 may have an anxiolytic effect, influencing behavior and CRF levels in the amygdala following acute stress. In a rat model of predator-induced stress, SB-408124 treatment exhibited behavioral changes, including increased grooming acts and altered exploratory behavior. SB-408124 led to changes in corticotropin-releasing factor (CRF) levels in the amygdala. SB-408124 prevented the CRF level decrease induced by stress. Reference: Georgian Med News. 2019 May;(290):127-131. https://pubmed.ncbi.nlm.nih.gov/31322529/

	Solvent	mg/mL	mM
Solubility
	DMSO	35.6	100.00

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 356.38 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. Langmead CJ, Jerman JC, Brough SJ, Scott C, Porter RA, Herdon HJ. Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br J Pharmacol. 2004 Jan;141(2):340-6. doi: 10.1038/sj.bjp.0705610. Epub 2003 Dec 22. PMID: 14691055; PMCID: PMC1574197. 2. Tissen I, Kurbanov R, Hohlov K, Proshin S, Lebedev A, Bagaturiya G, Shabanov P. OX1R ANTAGONIST SB408124 ACTION AND EXTRAHYPOTHALAMIC CRF IN RATS AFTER PSYCHOTRAUMATIC EXPOSURE. Georgian Med News. 2019 May;(290):127-131. PMID: 31322529. 3. Ibrahim BM, Abdel-Rahman AA. A pivotal role for enhanced brainstem Orexin receptor 1 signaling in the central cannabinoid receptor 1-mediated pressor response in conscious rats. Brain Res. 2015 Oct 5;1622:51-63. doi: 10.1016/j.brainres.2015.06.011. Epub 2015 Jun 18. PMID: 26096126; PMCID: PMC4562882.

In vitro protocol:

In vivo protocol:

1. Tissen I, Kurbanov R, Hohlov K, Proshin S, Lebedev A, Bagaturiya G, Shabanov P. OX1R ANTAGONIST SB408124 ACTION AND EXTRAHYPOTHALAMIC CRF IN RATS AFTER PSYCHOTRAUMATIC EXPOSURE. Georgian Med News. 2019 May;(290):127-131. PMID: 31322529. 2. Ibrahim BM, Abdel-Rahman AA. A pivotal role for enhanced brainstem Orexin receptor 1 signaling in the central cannabinoid receptor 1-mediated pressor response in conscious rats. Brain Res. 2015 Oct 5;1622:51-63. doi: 10.1016/j.brainres.2015.06.011. Epub 2015 Jun 18. PMID: 26096126; PMCID: PMC4562882.

1: Langmead CJ, Jerman JC, Brough SJ, Scott C, Porter RA, Herdon HJ. Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br J Pharmacol. 2004 Jan;141(2):340-6. doi: 10.1038/sj.bjp.0705610. Epub 2003 Dec 22. PMID: 14691055; PMCID: PMC1574197. 2: Tissen I, Kurbanov R, Hohlov K, Proshin S, Lebedev A, Bagaturiya G, Shabanov P. OX1R ANTAGONIST SB408124 ACTION AND EXTRAHYPOTHALAMIC CRF IN RATS AFTER PSYCHOTRAUMATIC EXPOSURE. Georgian Med News. 2019 May;(290):127-131. PMID: 31322529. 3: Morairty SR, Revel FG, Malherbe P, Moreau JL, Valladao D, Wettstein JG, Kilduff TS, Borroni E. Dual hypocretin receptor antagonism is more effective for sleep promotion than antagonism of either receptor alone. PLoS One. 2012;7(7):e39131. doi: 10.1371/journal.pone.0039131. Epub 2012 Jul 2. PMID: 22768296; PMCID: PMC3388080. 4: Valiante S, Liguori G, Tafuri S, Pavone LM, Campese R, Monaco R, Iachetta G, Assisi L, Mirabella N, Forte M, Costagliola A, Vittoria A. Expression and potential role of the peptide orexin-A in prostate cancer. Biochem Biophys Res Commun. 2015 Sep 4;464(4):1290-1296. doi: 10.1016/j.bbrc.2015.07.124. Epub 2015 Jul 26. PMID: 26220343. 5: Shoblock JR, Welty N, Aluisio L, Fraser I, Motley ST, Morton K, Palmer J, Bonaventure P, Carruthers NI, Lovenberg TW, Boggs J, Galici R. Selective blockade of the orexin-2 receptor attenuates ethanol self-administration, place preference, and reinstatement. Psychopharmacology (Berl). 2011 May;215(1):191-203. doi: 10.1007/s00213-010-2127-x. Epub 2010 Dec 22. PMID: 21181123. 6: Melis MR, Sanna F, Succu S, Ferri GL, Argiolas A. Neuroendocrine regulatory peptide-1 and neuroendocrine regulatory peptide-2 influence differentially feeding and penile erection in male rats: sites of action in the brain. Regul Pept. 2012 Aug 20;177(1-3):46-52. doi: 10.1016/j.regpep.2012.04.007. Epub 2012 May 2. PMID: 22561139. 7: Messal N, Fernandez N, Dayot S, Gratio V, Nicole P, Prochasson C, Chantret I, LeGuilloux G, Jarry A, Couvelard A, Tréton X, Voisin T, Ogier-Denis E, Couvineau A. Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3618-3628. doi: 10.1016/j.bbadis.2018.08.023. Epub 2018 Aug 18. PMID: 30251681. 8: Bonaventure P, Yun S, Johnson PL, Shekhar A, Fitz SD, Shireman BT, Lebold TP, Nepomuceno D, Lord B, Wennerholm M, Shelton J, Carruthers N, Lovenberg T, Dugovic C. A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal without hypnotic effects. J Pharmacol Exp Ther. 2015 Mar;352(3):590-601. doi: 10.1124/jpet.114.220392. Epub 2015 Jan 12. PMID: 25583879; PMCID: PMC4352589. 9: Ibrahim BM, Abdel-Rahman AA. A pivotal role for enhanced brainstem Orexin receptor 1 signaling in the central cannabinoid receptor 1-mediated pressor response in conscious rats. Brain Res. 2015 Oct 5;1622:51-63. doi: 10.1016/j.brainres.2015.06.011. Epub 2015 Jun 18. PMID: 26096126; PMCID: PMC4562882. 10: Hurley SW, Arseth HA, Johnson AK. Orexin neurons couple neural systems mediating fluid balance with motivation-related circuits. Behav Neurosci. 2018 Aug;132(4):284-292. doi: 10.1037/bne0000250. Epub 2018 Jun 28. PMID: 29952605; PMCID: PMC6446920. 11: Patel VH, Karteris E, Chen J, Kyrou I, Mattu HS, Dimitriadis GK, Rodrigo G, Antoniades C, Antonopoulos A, Tan BK, Hillhouse EW, Ng A, Randeva HS. Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection. Clin Sci (Lond). 2018 Dec 13;132(24):2547-2564. doi: 10.1042/CS20180150. PMID: 30467191; PMCID: PMC6365625. 12: Aldridge GM, Zarin TA, Brandner AJ, George O, Gilpin NW, Repunte-Canonigo V, Sanna PP, Koob GF, Vendruscolo LF, Schmeichel BE. Effects of single and dual hypocretin-receptor blockade or knockdown of hypocretin projections to the central amygdala on alcohol drinking in dependent male rats. Addict Neurosci. 2022 Sep;3:100028. doi: 10.1016/j.addicn.2022.100028. Epub 2022 Jul 3. PMID: 35965958; PMCID: PMC9365098. 13: Malherbe P, Borroni E, Pinard E, Wettstein JG, Knoflach F. Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists. Mol Pharmacol. 2009 Sep;76(3):618-31. doi: 10.1124/mol.109.055152. Epub 2009 Jun 19. PMID: 19542319. 14: Mould R, Brown J, Marshall FH, Langmead CJ. Binding kinetics differentiates functional antagonism of orexin-2 receptor ligands. Br J Pharmacol. 2014 Jan;171(2):351-63. doi: 10.1111/bph.12245. PMID: 23692283; PMCID: PMC3904256. 15: Xiao F, Jiang M, Du D, Xia C, Wang J, Cao Y, Shen L, Zhu D. Orexin A regulates cardiovascular responses in stress-induced hypertensive rats. Neuropharmacology. 2013 Apr;67:16-24. doi: 10.1016/j.neuropharm.2012.10.021. Epub 2012 Nov 9. PMID: 23147417. 16: Girault EM, Foppen E, Ackermans MT, Fliers E, Kalsbeek A. Central administration of an orexin receptor 1 antagonist prevents the stimulatory effect of Olanzapine on endogenous glucose production. Brain Res. 2013 Aug 21;1527:238-45. doi: 10.1016/j.brainres.2013.06.034. Epub 2013 Jul 4. PMID: 23830851. 17: Woldan-Tambor A, Biegańska K, Wiktorowska-Owczarek A, Zawilska JB. Activation of orexin/hypocretin type 1 receptors stimulates cAMP synthesis in primary cultures of rat astrocytes. Pharmacol Rep. 2011;63(3):717-23. doi: 10.1016/s1734-1140(11)70583-7. PMID: 21857082. 18: Toyama S, Shimoyama N, Shimoyama M. The analgesic effect of orexin-A in a murine model of chemotherapy-induced neuropathic pain. Neuropeptides. 2017 Feb;61:95-100. doi: 10.1016/j.npep.2016.12.007. Epub 2016 Dec 24. PMID: 28041630. 19: Assisi L, Tafuri S, Liguori G, Paino S, Pavone LM, Staiano N, Vittoria A. Expression and role of receptor 1 for orexins in seminiferous tubules of rat testis. Cell Tissue Res. 2012 Jun;348(3):601-7. doi: 10.1007/s00441-012-1394-8. Epub 2012 Mar 28. PMID: 22450910. 20: Corcoran A, Richerson G, Harris M. Modulation of respiratory activity by hypocretin-1 (orexin A) in situ and in vitro. Adv Exp Med Biol. 2010;669:109-13. doi: 10.1007/978-1-4419-5692-7_22. PMID: 20217331; PMCID: PMC3858080.