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Purity: ≥98%
GW-274150 is a novel, potent, arginine-competitive,highly selective, NADPH-dependent, and long-acting inhibitor of inducible nitric oxide synthase (iNOS) activity in rat and mouse models of renal I/R. GW274150 was identified from a series of acetamide amino acids that have a high selectivity for iNOS vs both eNOS (> 260-fold) and nNOS (> 219-fold) and high bioavailability (> 90%) after oral administration. GW274150 reduced histologic evidence of tubular injury and markedly reduced immunohistochemical evidence of nitrotyrosine and PAR formation, indicating reduced peroxynitrite formation and poly (ADP-ribose) polymerase (PARP) activation, respectively. It may be helpful in treating renal dysfunction and injury associated with I/R of the kidney.
ln Vitro |
J774 cells' intracellular iNOS is inhibited by GW274150 in a time-dependent manner, with an IC50 value of 0.2 μM [1]. In rat tissues, GW274150 exhibits 260- and 219-fold selectivity for iNOS relative to eNOS and nNOS, respectively. In comparison to human eNOS and nNOS, human iNOS exhibits >100- and >80-fold increases, respectively [1].
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ln Vivo |
One intraperitoneal injection of GW274150, a long-acting (rat half-life of 5 hours) iNOS inhibitor, can prevent LPS-mediated increases in plasma NO2- and NO3-levels 14 hours later (ED50=3 mg/kg) [2]. In a dose-related manner, GW274150 (intraperitoneal injection; 2.5, 5, and 10 mg/kg) lessens the extent of lung injury caused by carrageenan. Edema development and neutrophil infiltration in the pleural space were also markedly and dose-dependently reduced in rats [2]. When taken orally (30 mg/kg, twice daily, for seven days), GW274150 significantly protects neurons; however, in Parkinson's disease (PD), it has a neuroprotective effect that resembles a bell when combined with 6-OHDA. In mouse models, it is ineffective at high doses [3].
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Animal Protocol |
Animal/Disease Models: SD-rat [2]
Doses: 2.5, 5 and 10 mg/kg; single dose Route of Administration: intraperitoneal (ip) injection 5 minutes before carrageenan injection Experimental Results: Protection against carrageenan-induced acute inflammation model of lung injury effect. |
References |
[1]. Alderton WK, et al. GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo.Br J Pharmacol. 2005 Jun;145(3):301-12.
[2]. Dugo L, et al. Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation. Br J Pharmacol. 2004 Mar;141(6):979-87. Epub 2004 Feb [3]. Broom L, et al. Neuroprotection by the selective iNOS inhibitor GW274150 in a model of Parkinson disease.Free Radic Biol Med. 2011 Mar 1;50(5):633-40. |
Molecular Formula |
C8H16N2O3S
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Molecular Weight |
220.28924
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CAS # |
210354-22-6
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Related CAS # |
GW274150 phosphate;438542-15-5;GW274150 dihydrochloride;438542-17-7
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
CC(=N)NCCSCC[C@@H](C(=O)O)N
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InChi Key |
MOLOJNHYNHBPCW-ZETCQYMHSA-N
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InChi Code |
InChI=1S/C8H17N3O2S/c1-6(9)11-3-5-14-4-2-7(10)8(12)13/h7H,2-5,10H2,1H3,(H2,9,11)(H,12,13)/t7-/m0/s1
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Chemical Name |
L-Homocysteine, S-(2-((1-iminoethyl)amino)ethyl)-
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Synonyms |
GW-274150; GW 274150; GW274150.
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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 : ~100 mg/mL (~456.00 mM)
H2O : ≥ 62 mg/mL (~282.72 mM) |
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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 | 4.5395 mL | 22.6974 mL | 45.3947 mL | |
5 mM | 0.9079 mL | 4.5395 mL | 9.0789 mL | |
10 mM | 0.4539 mL | 2.2697 mL | 4.5395 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.