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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
SB-674042 is a novel, potent and selective non-peptide orexin OX1 receptor antagonist with Kd of 3.76 nM; It exhibits 100-fold selectivity for OX1 over OX2 receptors. The control of arousal and the sleep-wake cycle is mediated by orexins and their receptors. Almorexant is a dual OX antagonist that has been shown to be effective in both promoting and sustaining sleep in clinical studies. The structural basis for pharmacologic selectivity between OX(1) and OX(2) is provided by the local conformation of helix positions 3.32, 3.33, and 3.36 in transmembrane domain 3 and 45.51 in ECL2b, despite the high degree of similarity in the ligand-binding pockets of OX(1) and OX(2) and the numerous aromatic/hydrophobic interactions.
Targets |
OX1 Receptor ( IC50 = 3.76 nM ); OX2 Receptor ( IC50 = 531 nM ); OX1 Receptor ( Ki = 1.1 nM ); OX2 Receptor ( Ki = 129 nM )
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ln Vitro |
SB-674042 ([3H]) (0.2-24 nM; 2 h) has a high affinity and can be used as a radioligand to identify human OX1 receptors that are consistently expressed in CHO cells[1].
SB-674042 (5 μM; 4 ℃ for 30 min, and 37 ℃ for 3 h) decreases the ability of the CB1 receptor agonist (HY-14137) to phosphorylate ERK1/2 in HEK293 cells co-expressing the orexin-1 and CB1 receptors[2]. SB-674042 (1 μM; 24 h) eliminates the rise in mTOR phosphorylation in INS-1 cells in response to Orexin-A (HY-106224) (1 nM-1 μM; 24 h), suggesting that the activated OX1 receptor was necessary for the mTOR pathway to be activated by Orexin-A[3]. |
ln Vivo |
SB-674042 (0.3 nM/0.3 μL; icv; single dose) decreases contextual and cues fear freezing responses in Stay animals in the Stress Alternatives Model (SMA) in mice[4].
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Cell Assay |
Cell Line: INS-1 cells
Concentration: 1 μM Incubation Time: 24 hours; accompanied with 1 μM Orexin-A for 24 hour Result: Decreased the phosphorylation level of mTOR induced by Orexin-A |
Animal Protocol |
Stress-induced mice model (male C57BL/6NHsd mice, 22-26 g)
0.3 nM/0.3 μL Intracerebroventricular injection; subjected mice to 4 days of social aggression (days 1-4) |
References |
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Molecular Formula |
C24H21FN4O2S
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Molecular Weight |
448.51254
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Exact Mass |
448.14
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Elemental Analysis |
C, 64.27; H, 4.72; F, 4.24; N, 12.49; O, 7.13; S, 7.15
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CAS # |
483313-22-0
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Appearance |
Solid powder
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SMILES |
CC1=NC(=C(S1)C2=CC=CC=C2F)C(=O)N3CCC[C@H]3CC4=NN=C(O4)C5=CC=CC=C5
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InChi Key |
HYBZWVLPALMACV-KRWDZBQOSA-N
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InChi Code |
InChI=1S/C24H21FN4O2S/c1-15-26-21(22(32-15)18-11-5-6-12-19(18)25)24(30)29-13-7-10-17(29)14-20-27-28-23(31-20)16-8-3-2-4-9-16/h2-6,8-9,11-12,17H,7,10,13-14H2,1H3/t17-/m0/s1
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Chemical Name |
[5-(2-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]-[(2S)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]pyrrolidin-1-yl]methanone
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Synonyms |
SB-674042; SB 674042; SB674042
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: ~25 mg/mL (~55.7 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.43 mg/mL (3.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.43 mg/mL (3.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.43 mg/mL (3.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.2296 mL | 11.1480 mL | 22.2960 mL | |
5 mM | 0.4459 mL | 2.2296 mL | 4.4592 mL | |
10 mM | 0.2230 mL | 1.1148 mL | 2.2296 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Total, specific and nonspecific binding of [3H]SB-674042 to (a) CHO-K1 whole cells stably expressing the OX1 receptor and (b) membranes from CHO-K1 cells expressing the OX1 receptor in SPA format, with increasing radioligand concentration. Br J Pharmacol . 2004 Jan;141(2):340-6. td> |
Time course for association and dissociation of [3H]SB-674042 binding to CHO-K1_OX1 whole cells. Br J Pharmacol . 2004 Jan;141(2):340-6. td> |
Orexin A causes phosphorylation of ERK MAP kinases via VSV-G-h-orexin-1-eYFP and internalization of this construct; SB-674042 is an orexin-1 receptor antagonist. J Biol Chem . 2006 Dec 15;281(50):38812-24. td> |
SR-141716A and SB-674042 are highly selective pharmacological reagents. a, the specific binding of [3H]SR-141716A (5 nm) in the absence or presence of orexin A (OXA) (0.5 μm) or SB-674042 (5 μm) was assessed in membranes of cells constitutively expressing h-CB-1 without induction of VSV-G-h-orexin-1-eYFP. J Biol Chem . 2006 Dec 15;281(50):38812-24. td> |