| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary molecular target of GSK 189254 HCl is the histamine H3 receptor, a presynaptic G protein-coupled receptor that regulates the release of histamine and other neurotransmitters in the brain. By blocking the H3 receptor, GSK 189254 HCl increases the release of acetylcholine, noradrenaline, and dopamine in the anterior cingulate cortex and acetylcholine in the dorsal hippocampus. This modulation of neurotransmitter release underlies its procognitive and wake-promoting effects.
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|---|---|
| ln Vitro |
In vitro, GSK 189254 HCl is a high-affinity H3 receptor antagonist with pKi values of 9.59-9.90 for human H3 and 8.51-9.17 for rat H3. It binds to recombinant H3 receptors expressed in HEK-293-MSR-II cells and native H3 receptors in the cerebral cortex of several species. The compound exhibits higher affinity for human and pig H3 receptors compared to rat, mouse, and dog H3 receptors.
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| ln Vivo |
In vivo, GSK 189254 HCl (0.3-3 mg/kg p.o.) increases the release of acetylcholine, noradrenaline, and dopamine in the anterior cingulate cortex and acetylcholine in the dorsal hippocampus. It significantly improves performance in diverse cognition paradigms in rats, including passive avoidance, water maze, object recognition, and attentional set shift. In orexin knockout mice, it reduces narcoleptic episodes and modulates sleep-wake activity.
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| Enzyme Assay |
Non-cell-based assays for GSK 189254 HCl use radioligand binding with [3H]GSK189254 in membrane preparations from cells expressing recombinant H3 receptor or rat brain cortex. Membranes are incubated with radioligand and increasing concentrations of test compounds in assay buffer. Bound radioligand is separated by rapid filtration, and radioactivity is quantified. IC50 values are determined from dose-response curves.
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| Cell Assay |
Cell-based assays for GSK 189254 HCl use H3 receptor-expressing cell lines such as HEK293-H3R or CHO-H3R. Cells are cultured in standard medium, and H3 receptor-mediated signaling is measured by cAMP inhibition assay or [35S]GTPγS binding. GSK 189254 HCl is added at varying concentrations to determine antagonist potency.
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| Animal Protocol |
In vivo protocols for GSK 189254 HCl use rats or mice for cognitive and sleep studies. The compound is administered orally at doses ranging from 0.3 to 3 mg/kg. Cognitive function is assessed by passive avoidance, water maze, object recognition, and attentional set shift tests. Sleep-wake activity is measured by EEG/EMG recordings. Neurotransmitter release is measured by microdialysis.
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| References |
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| Molecular Formula |
C21H25N3O2.HCL
|
|---|---|
| Molecular Weight |
387.90304
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| Exact Mass |
387.171
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| CAS # |
945493-87-8
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| Related CAS # |
945493-87-8 (HCl);720690-73-3;
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| PubChem CID |
24768876
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.501
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| tPSA |
57.95
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
482
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CNC(C1=CN=C(OC2=CC=C3CCN(C4CCC4)CCC3=C2)C=C1)=O.Cl
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| InChi Key |
GRQVZNMSXFEEHD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H25N3O2.ClH/c1-22-21(25)17-6-8-20(23-14-17)26-19-7-5-15-9-11-24(18-3-2-4-18)12-10-16(15)13-19;/h5-8,13-14,18H,2-4,9-12H2,1H3,(H,22,25);1H
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| Chemical Name |
6-[(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)oxy]-N-methylpyridine-3-carboxamide;hydrochloride
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5780 mL | 12.8899 mL | 25.7798 mL | |
| 5 mM | 0.5156 mL | 2.5780 mL | 5.1560 mL | |
| 10 mM | 0.2578 mL | 1.2890 mL | 2.5780 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.
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