| 名稱 | MK-886 |
| 描述 | MK-886 (L 663536) is an inhibitor of leukotriene biosynthesis, inhibiting 5-lipoxygenase-activating protein (FLAP). It is also a moderately potent PPARα antagonist. |
| 細胞實驗 | IL-1β-stimulated A549 cells (5×106/ml) are pre-incubated with MK-886 (MK, 33 μM), indomethacin (Indo, 10 μM), celecoxib (Cele, 5 μM) or vehicle (DMSO) for 15 min prior to the addition of 30 μM arachidonic acid. After 15 min at 37 °C, the amount of released 6-keto PGF1α was assessed by ELISA as described in the Materials and methods section. (Only for Reference) |
| 激酶實驗 | Enzyme assay is conducted in buffer containing 25 mM Tris, pH 8.0, 1 mM DTT, 1 mM spermine, 50 mM KCl, 0.01% Nonidet P-40, and 1 mM MgCl2. PARP reaction contains 0.1 μCi [3H]NAD+ (200 000 DPM), 1.5 μM NAD+, 150 nM biotinylated NAD+, 1 μg/mL activated calf thymus, and 1?5 nM PARP-1. Autoreactions utilizing SPA bead-based detection are carried out in 50 μL volumes in white 96-well plates. Compounds (e.g., MK-4827) are prepared in 11-point serial dilution in 96-well plate, 5 μL/well in 5% DMSO/Water (10× concentrated). Reactions are initiated by adding first 35 μL of PARP-1 enzyme in buffer and incubating for 5 min at room temperature and then 10 μL of NAD+ and DNA substrate mixture. After 3 h at room temperature, these reactions are terminated by the addition of 50 μL of streptavidin-SPA beads (2.5 mg/mL in 200 mM EDTA, pH 8). After 5 min, they are counted using a TopCount microplate scintillation counter. IC50 data is determined from inhibition curves at various substrate concentrations[1]. |
| 體外活性 | MK-886是一種抑制5-脂氧合酶激活蛋白(FLAP)的化合物，能強效抑制完整細胞內(nèi)的白三烯生物合成，常用于確定5-脂氧合酶(EC 1.13.11.34)途徑在細胞或動物模型中對炎癥、過敏、癌癥和心血管疾病的作用。MK-886對分離的COX-1的抑制作用（IC50=8 μM），可以阻斷由COX-1衍生的產(chǎn)物12(S)-羥基-5-順-8,10-反-十七碳三烯酸(12-HHT)和血栓素B2在人類洗滌血小板中對膠原蛋白以及外源性花生四烯酸的響應中的形成（IC50=13–15 μM）。分離的COX-2受到的影響較?。↖C50=58 μM），在A549細胞中，MK-886（33 μM）未能抑制COX-2依賴的6-酮前列腺素（PG）F1α的形成。MK-886（10 μM）能抑制COX-1介導的血小板聚集反應，該反應由膠原蛋白或花生四烯酸誘導，而由凝血酶或U-46619（COX獨立）誘導的聚集并不受影響[1]。 |
| 體內(nèi)活性 | 連續(xù)每日通過腹腔注射MK-886會增加從前額葉皮層獲取的大腦樣本中GluR1的磷酸化水平。相比之下，單次注射MK-886并不改變大腦皮質(zhì)GluR1的磷酸化水平[2]。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.24 mM), Sonication is recommended.
Ethanol : 2.4 mg/mL (5.08 mM), Sonication is recommended.
DMSO : 117.5 mg/mL (248.9 mM), Sonication is recommended.
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| 關鍵字 | PPARα | PPAR | Peroxisome proliferator-activated receptors | non-competitive | MK-886 | MK 886 | LeukotrieneReceptor | Leukotriene Receptor | leukotriene | L-663536 | L663536 | keratin-1 | Inhibitor | inhibit | FLAP | COX-2 | COX-1 | biosynthesis | Apoptosis | 5-LOX | 5-LO activating protein |
| 相關產(chǎn)品 | Trometamol | Urea | Daidzein | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Dextran sulfate sodium salt (MW 5000) | Citric Acid Triammonium | Stavudine | Tamoxifen |
| 相關庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 已知活性化合物庫 | 抗衰老化合物庫 | 非甾體類抗炎化合物庫 | GPCR靶點分子庫 | 糖代謝化合物庫 | 免疫/炎癥分子化合物庫 | 膜蛋白靶向化合物庫 | 疼痛相關化合物庫 | 抗代謝疾病化合物庫 |