LY2608204

• 产品号: S2155
• CAS号: 1234703-40-2
• 分子式: C28H37N3O3S3
• 分子量: 559.80668
• 保 存: -20°C

产品别名

• 标题: LY2608204
• IUPAC标准名: (1R,2S)-2-cyclohexyl-1-[4-(cyclopropanesulfonyl)phenyl]-N-(5-{[2-(pyrrolidin-1-yl)ethyl]sulfanyl}-1,3-thiazol-2-yl)cyclopropane-1-carboxamide
• IUPAC传统名: (1R,2S)-2-cyclohexyl-1-[4-(cyclopropanesulfonyl)phenyl]-N-(5-{[2-(pyrrolidin-1-yl)ethyl]sulfanyl}-1,3-thiazol-2-yl)cyclopropane-1-carboxamide

产品登记号

• CAS号: 1234703-40-2

产品性质

• 成盐信息: Free Base
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Metabolic Disease

Biological Activity

• Description: LY2608204 activates glucokinase (GK) with EC50 of 42 nM.
• Targets: GK
• IC50: 42 nM (EC50) ^[1]
• In Vitro: LY2608204 activates glucokinase (GK) with EC50 of 42 nM at 10 mM glucose with a concentration dependent manner at lower glucose concentrations. LY2608204 also stimulates glucose metabolism in rat insulinoma INS1-E cells with EC50 of 579 nM. ^[1]
• In Vivo: LY2608204 decreases plasma glucose in a dose-dependent manner at both fasted and postprandial glucose levels. A maximal lowering of glucose AUC versus the untreated control group is observed with the high dose (30 mg/kg) and represents a 42% decrease. Interpolation of the data show that a 20% glucose AUC decrease occurs at an average LY2608204 concentration of 99 ng/mL (179 nM) in plasma, corresponding to a 6.9 mg/kg LY2608204 dose. The in vivo blood brain barrier permeability of LY2608204 results in a mean brain/plasma ratio of 0.17 five minutes post-dose with a mean total brain level of 0.539 nmol/g. ^[1]

Protocol

• Protocol: Kinase Assay ^[1]
• Glucokinase assay: The human islet GK isoform is expressed in E. coli as (His)₆-tagged fusion protein and purified with metal chelate affinity chromatography. After purification the enzyme is stored in aliquots at concentration 0.8 mg/mL in 25 mM sodium phosphate, 150 mM sodium chloride, 100 mM imidazole, 1 mM dithiothreitol, 50% glycerol at ?80 °C. The assay is performed in flat bottom 96-well plates in a final incubation volume of 100 μL. The incubation mixture consists of 25 mM HEPES (pH7.4), 50 mM potassiumchloride, 2.5 mM magnesiumchloride, 2 mM dithiothreitol, 4 U/mL glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides, 5 mM ATP, 1 mM NAD and a set concentration of glucose. LY2608204 is dissolved in DMSO and then added to the reaction mixture giving the final DMSO concentration of 10%. The reaction is initiated by addition of 20 μL GK and runs for 20 min at 37 °C. The amount of formed NADH is measured as an increase in absorbance at 340 nm using a microplate reader. Absorbance values are used for EC50 calculations.
• Protocol: Animal Study ^[1]
• Animal Models: Male Wistar rats at a weight of 225-250 g
• Formulation: LY2608204 is suspended in a 1:1 mixture of solutol/ethanol in a bath sonicator (10% of total volume). The obtained suspension is then diluted with 9 volumes of 10% aqueous solutol solution.
• Doses: 1, 3, 6, 10, 20 and 30 mg/kg
• Administration: Orally, rats are given a 2 g/kg oral glucose bolus 2 hours after LY2608204 administration.

References

• References: [1] US Patent, 8063079, 2011.

参考文献

• US Patent, 8063079, 2011.