Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Sitagliptin (MK0431) 是一种有效的 DPP4抑制剂,在 Caco-2 细胞中,IC50值为 19 nM。它是一种新型口服降糖药,可单独使用或与二甲双胍或噻唑烷二酮联合用于治疗 2 型糖尿病。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
50 mg | ¥ 515 | 现货 | ||
100 mg | ¥ 722 | 现货 | ||
200 mg | ¥ 996 | 现货 |
产品描述 | Sitagliptin (MK0431), a new oral hypoglycemic (anti-diabetic drug), is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. This enzyme-inhibiting drug is used either alone or in combination with metformin or thiazolidinedione for treatment of type 2 diabetes mellitus. The drug can competitively inhibit a protein/enzyme and DPP-4, that leads to an incremental amount of active incretins (GLP-1 and GIP), the diminished amount of release of glucagon and increased release of insulin. |
靶点活性 | DPP4:18 nM |
体外活性 | Sitagliptin phosphate 对 DPP-4 具有强效抑制作用,从 Caco-2 细胞提取物中提取的 IC50 为 19 nM[1]。Sitagliptin phosphate 通过 cAMP/PKA/Rac1 激活途径减少离体脾脏 CD4 T 细胞的体外迁移[2]。Sitagliptin phosphate 通过一种不依赖于 DPP-4、蛋白激酶 A 和 MEK-ERK1/2 的途径发挥一种新的直接作用,刺激肠 L 细胞分泌 GLP-1。Sitagliptin phosphate 能降低自身免疫对移植物存活率的影响[3]。 |
体内活性 | Sitagliptin phosphate 对自由采食的汉-Wistar 大鼠血浆中 DPP-4 活性的抑制 ED50 值为剂量后 7 小时 2.3 mg/kg和剂量后 24 小时 30 mg/kg[1]。链脲佐菌素诱导的 1 型糖尿病小鼠模型显示血浆中的 DPP-4 水平升高,而Sitagliptin phosphate 饮食可大幅抑制这种升高。这可能是通过延长胰岛移植存活时间对高血糖的调节产生积极影响而实现的[4]。Sitagliptin phosphate 在大鼠体内的血浆清除率和分布容积(40-48 mL/min/kg,7-9 L/kg)高于狗(9 mL/min/kg,3 L/kg);在大鼠体内的半衰期为 2 小时,短于狗的 4 小时[5]。 |
激酶实验 | DPP-4 is extracted from confluent Caco-2 cells. After 5 minutes of incubation at room temperature with lysis buffer (10 mM Tris-HCl, 150 mM NaCl, 0.04 U/mL aprotinin, 0.5% Nonidet P40, pH 8.0), cells are centrifuged at 35,000 g at 4°C for 30 minutes, and the supernatant is stored at -80°C. Assays are performed by mixing 20 μL of appropriate compound dilutions with 50 μL of the substrate for the DPP-4 enzyme, H-Ala-Pro-7-amido-4-trifluoromethylcoumarin (final concentration in the assay, 100 μM) and 30 μL of the Caco-2 cell extract (diluted 1000-fold with 100 mM Tris-HCl, 100 mM NaCl, pH 7.8). Plates are incubated at room temperature for 1 hour, and fluorescence is measured at excitation/emission wavelengths of 405/535 nm using a SpectraMax GeminiXS. Dissociation kinetics of inhibitors from the DPP-4 enzyme is determined after a 1-hour preincubation of Caco-2 cell extracts with high inhibitor concentrations (30 nM for BI 1356, 3 μM for vildagliptin). The enzymatic reaction is started by adding the substrate H-Ala-Pro-7-amido-4-trifluoromethylcoumarin after a 3000-fold dilution of the preincubation mixture with assay buffer. Under these conditions, the difference in DPP-4 activity at a certain time point in the presence or absence of an inhibitor reflects the amount of this inhibitor still bound to the DPP-4 enzyme. Maximal reaction rates (fluorescence units/seconds ×1000) at 10-minute intervals are calculated using the SoftMax software of the SpectraMax and corrected for the rate of an uninhibited reaction [(vcontrol-vinhibitor)/vcontrol]. |
细胞实验 | CD4T-cells are plated on membrane inserts in serum-free RPMI 1640, and cell migration is assayed using Transwell chambers (Corning), in the presence or absence of purified porcine kidney DPP-4 (32.1 units/mg; 100 mU/mL final concentration) and DPP-4 inhibitor (100 μM). After 1 hour, cells on the upper surface are removed mechanically, and cells that have migrated into the lower compartment are counted. The extent of migration is expressed relative to the control sample. |
别名 | 西他列汀, MK0431, 西格列汀 |
分子量 | 407.31 |
分子式 | C16H15F6N5O |
CAS No. | 486460-32-6 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 198.9 mM
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.4551 mL | 12.2757 mL | 24.5513 mL | 61.3783 mL |
5 mM | 0.491 mL | 2.4551 mL | 4.9103 mL | 12.2757 mL | |
10 mM | 0.2455 mL | 1.2276 mL | 2.4551 mL | 6.1378 mL | |
20 mM | 0.1228 mL | 0.6138 mL | 1.2276 mL | 3.0689 mL | |
50 mM | 0.0491 mL | 0.2455 mL | 0.491 mL | 1.2276 mL | |
100 mM | 0.0246 mL | 0.1228 mL | 0.2455 mL | 0.6138 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Sitagliptin 486460-32-6 Autophagy Proteases/Proteasome Ubiquitination Proteasome DPP-4 Dipeptidyl Peptidase MK-0431 西他列汀 inhibit MK0431 MK 0431 Inhibitor 西格列汀 DPP inhibitor