| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
MCH R1/melanin-concentrating hormone receptor 1 (pIC50 = 9.3)
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| ln Vitro |
The MCH-induced MCHR1 receptor is highly active against GW-803430, with an IC50 value of about 13 nM [2].
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| ln Vivo |
In comparison to the vehicle control, GW-803430 (0.3, 3, and 15 mg/kg; oral; once daily) produced a sustained dose-dependent weight decrease [1]. Because of its favorable pharmacokinetic characteristics in mice (bioavailability = 31%, t1/2 = 11 h) and brain penetration (6:1 brain:plasma concentration), GW-803430 is an appropriate molecule [1].
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| Enzyme Assay |
Melanin Concentrating Hormone Receptor (MCHR 1 ) Assay. [2]
Antagonistic potential of N. nucifera extracts on MCHR1 receptor was studied using MCHR1 Gi coupled CHO-K1 cells. Cell density of 3 × 104 cells/well was plated in 96-well tissue culture plates containing cell plating reagent and incubated for 24 h. After incubation, the entire medium was aspirated and 45 μL of cell assay buffer and antibody mixture was added to each well. N. nucifera or reference antagonist (GW 803430) was added to the respective wells and incubated for 15 min at 37°C and 5% CO2. Agonist compound (MCH—62.5 nM + Forskolin 20 μM) was added to the respective wells and incubated for 30 min. 60 μL of prepared detection reagent solution and cAMP solution D was added to each well and incubated for 60 min at room temperature in the dark. 60 μL of cAMP Solution A was added and incubated for 3 hr at room temperature in the dark. Plate was read using luminescence plate reader (FLUOstar). |
| Cell Assay |
The compounds were assayed for MCH R1 functional antagonist activity as described in WO 2004/092181 A1 (corrected version), pp 215–216. CHO cells expressing an elkgal4-luc+ reporter gene (host) were transfected with human MCH R1. The ability of the antagonists to inhibit an EC80 response of MCH was assessed via a TopCount microplate scintillation counter (Packard) and the specificity of the MCH R1 response was determined by measuring the ability of the antagonists to inhibit an EC80 thrombin response in the host cells. All compounds were assayed with n ⩾ 4. [1]
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| Animal Protocol |
Animal/Disease Models: High-fat diet-induced obese AKR/J mice [1]
Doses: 0.3, 3, and 15 mg/kg Route of Administration: Orally, one time/day for 12 days Experimental Results: Result in sustained dose-dependent weight loss of -6.2 %, relative to vehicle control, were -12.1% and -13.1% respectively. |
| References |
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| Additional Infomation |
Optimization of a series of constrained melanin-concentrating hormone receptor 1 (MCH R1) antagonists has provided compounds with potent and selective MCH R1 activity. Details of the optimization process are provided and the use of one of the compounds in an animal model of diet-induced obesity is presented. [1]
N. nucifera is one among the important medicinal plants assessed for its antiobesity action in various preclinical models. The present study was aimed at investigating the antiobesity effect of methanol and successive water extracts of petals of N. nucifera by studying its effect on adipogenesis, adipolysis, lipase, serotonin (5-HT2C), cannabinoid (CNR2), melanocyte concentrating hormone (MCHR1), and melanocortin (MC4R) receptors. Both methanol and successive water extracts of N. nucifera petals had an effect on inhibition of lipid storage in adipocytes and on increasing lipolysis. N. nucifera petal methanol extract exhibited the concentration-dependent inhibitory effect on lipase activity with an IC50 value of 47 µg/mL. N. nucifera petal extracts showed evident agonist and antagonist activity towards 5-HT2C and CNR2 receptors, respectively, while it showed no effect towards MCHR1 and MC4R receptors. Overall, methanol extract of N. nucifera petals showed better activity than successive water extract. [2] |
| Molecular Formula |
C25H24CLN3O3S
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|---|---|
| Molecular Weight |
481.995
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| Exact Mass |
481.123
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| Elemental Analysis |
C, 62.30; H, 5.02; Cl, 7.35; N, 8.72; O, 9.96; S, 6.65
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| CAS # |
515141-51-2
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| PubChem CID |
9826520
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| Appearance |
Off-white to yellow solid powder
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| LogP |
5.188
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
698
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MWULMTACIBZPGN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H24ClN3O3S/c1-31-22-14-19(8-9-21(22)32-13-12-28-10-2-3-11-28)29-16-27-20-15-23(33-24(20)25(29)30)17-4-6-18(26)7-5-17/h4-9,14-16H,2-3,10-13H2,1H3
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| Chemical Name |
6-(4-chlorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[3,2-d]pyrimidin-4-one
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| Synonyms |
GW803430; GW 803430; 515141-51-2; GW-3430; Thieno[3,2-d]pyrimidin-4(3H)-one, 6-(4-chlorophenyl)-3-[3-methoxy-4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-; 6-(4-chlorophenyl)-3-(3-methoxy-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)thieno[3,2-d]pyrimidin-4(3H)-one; GW803430; GW3430; CHEMBL214957; GW-803430
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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 | 2.0747 mL | 10.3734 mL | 20.7469 mL | |
| 5 mM | 0.4149 mL | 2.0747 mL | 4.1494 mL | |
| 10 mM | 0.2075 mL | 1.0373 mL | 2.0747 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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