SB-674042

Alias: SB-674042; SB 674042; SB674042

Cat No.:V4615 Purity: ≥98%

COA Product Data Instructions for use SDS

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.

SB-674042 Chemical Structure CAS No.: 483313-22-0
Product category: OX Receptor

This product is for research use only, not for human use. We do not sell to patients.

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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

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.

Biological Activity I Assay Protocols (From Reference)

Targets	OX₁ Receptor ( IC50 = 3.76 nM ); OX₂ Receptor ( IC50 = 531 nM ); OX₁ Receptor ( Ki = 1.1 nM ); OX₂ Receptor ( Ki = 129 nM )
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].
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	[1]. 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. [2]. Orexin-1 receptor-cannabinoid CB1 receptor heterodimerization results in both ligand-dependent and -independent coordinated alterations of receptor localization and function. J Biol Chem. 2006 Dec 15;281(50):38812-24. [3]. Orexin-A Stimulates Insulin Secretion Through the Activation of the OX1 Receptor and Mammalian Target of Rapamycin in Rat Insulinoma Cells. Pancreas. 2019 Apr;48(4):568-573. [4]. Orexin 1 Receptor Antagonism in the Basolateral Amygdala Shifts the Balance From Pro- to Antistress Signaling and Behavior. Biol Psychiatry. 2022 May 1;91(9):841-852.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C24H21FN4O2S
Molecular Weight	448.51254
Exact Mass	448.14
Elemental Analysis	C, 64.27; H, 4.72; F, 4.24; N, 12.49; O, 7.13; S, 7.15
CAS #	483313-22-0
Appearance	Solid powder
SMILES	CC1=NC(=C(S1)C2=CC=CC=C2F)C(=O)N3CCC[C@H]3CC4=NN=C(O4)C5=CC=CC=C5
InChi Key	HYBZWVLPALMACV-KRWDZBQOSA-N
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
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
Synonyms	SB-674042; SB 674042; SB674042
HS Tariff Code	2934.99.9001
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)

Solubility Data

Solubility (In Vitro)	DMSO: ~25 mg/mL (~55.7 mM)
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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: ~25 mg/mL (~55.7 mM)

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.
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 corn oil and mix evenly.

(Please use freshly prepared in vivo formulations for optimal results.)

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.

Calculator

Mass

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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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.

Note： (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.

Biological Data

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.

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.

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.

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.