| 名稱 | Fasiglifam |
| 描述 | Fasiglifam (TAK875) is a potent, selective and orally bioavailable GPR40 agonist. |
| 細胞實驗 | TAK-875 is dissolved in 1% BSA and 0.1% DMSO.? INS-1 832/13 cells are suspended in RPMI medium and seeded in a 96-well plate at a density of 2×104 cells/well; 1% BSA and 0.1% DMSO alone (control), palmitic acid (10, 100, and 1000 μM), oleic acid (10, 100, and 1000 μM), or TAK-875 (1, 10, and 100 μM) is added to the plate. After 72-h culture, medium is discarded, and cells are preincubated for 2 h with KRBH containing 1 mM glucose and 0.2% BSA at 37°C. After discarding of the preincubation buffer, KRBH containing 1 or 20 mM glucose and 0.2% BSA is added, and the plate is further incubated for 2 h. The insulin concentration in the supernatant is measured as described above. To measure intracellular insulin content, INS-1 832/13 cells are exposed to 1% BSA and 0.1% DMSO alone (control), palmitic acid (1000 μM), oleic acid (1000 μM), or TAK-875 (100 μM) with 1% BSA and 0.1% DMSO. After incubation, cells are washed once with phosphate-buffered saline, and acid-ethanol solution is added to each well, followed by sonication on ice. Intracellular insulin is extracted by overnight incubation at ?30°C, followed by separation of supernatant by centrifugation at 12,000 rpm×5 min at 4°C. |
| 激酶實驗 | INS-1 832/13 cells are suspended in RPMI medium containing 11 mM glucose and the supplements described above. These cells are seeded at a density of 2×104?cells/well in a 96-well black plate coated with poly-D-lysine, and 1% BSA and 0.1% DMSO alone (control), palmitic acid (62.5, 125, 250, 500, and 1000 μM), oleic acid (62.5, 125, 250, 500, and 1000 μM), or TAK-875 (6.25, 12.5, 25, 50, and 100 μM) is added to the plate with 1% BSA and 0.1% DMSO, followed by culture for 72 h. After the culture, caspase 3/7 activity is measured with the Apo-one homogeneous caspase 3/7 assay according to the manufacturer's instructions. Fluorescence intensity is measured at an excitation of 485 nm and an emission at 535 nm. |
| 體外活性 | Fasiglifam在CHO-hGPR40細胞中以濃度依賴的方式增加細胞內(nèi)IP產(chǎn)量，其EC50值為0.072 μM。在CHO細胞中，F(xiàn)asiglifam以濃度範(fàn)圍0.1-10 μM呈濃度依賴性提高細胞內(nèi)IP產(chǎn)量[1]。此外，F(xiàn)asiglifam在3-30 μM的濃度範(fàn)圍內(nèi)，依賴於濃度地增加[Ca2+]i。在10 mM葡萄糖存在的環(huán)境下，F(xiàn)asiglifam以0.001-10 μM的濃度範(fàn)圍內(nèi)，依賴於濃度地促進INS-1 833/15細胞中胰島素的分泌[2]。 |
| 體內(nèi)活性 | Fasiglifam（10 mg/kg，p.o.）在ZDF大鼠中提高了血漿胰島素水平。Fasiglifam（30 mg/kg，p.o.）改善了空腹高血糖，而不影響空腹正常血糖。與改善糖尿病大鼠葡萄糖耐量的劑量相比，F(xiàn)asiglifam在30 mg/kg的劑量，即3至10倍較高劑量，不會改變具有正常葡萄糖穩(wěn)態(tài)的SD大鼠的空腹血糖水平。同樣，F(xiàn)asiglifam在具有正常空腹血糖水平的SD大鼠中并未顯著改變胰島素分泌[1]。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 50 mg/mL (95.31 mM)
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| 關(guān)鍵字 | TAK 875 | inhibit | FFAR | Fasiglifam | Inhibitor | TAK-875 | Free Fatty Acid Receptor |
| 相關(guān)產(chǎn)品 | Benzyl nicotinate | CRTh2 antagonist 2 | CAY10595 | Azathioprine | Questiomycin A | TUG-1375 | NF-56-EJ40 | Monomethyl fumarate | 3-Hydroxyoctanoic Acid | Fezagepras sodium | Timapiprant | Vincamine |
| 相關(guān)庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 抗糖尿病庫 | NO PAINS 化合物庫 | 抗肥胖化合物庫 | GPCR靶點分子庫 | 膜蛋白靶向化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |