| 名称 | MK-0752 |
| 描述 | MK-0752, a γ-secretase inhibitor, reduces Aβ40 production(IC50=5 nM). |
| 激酶实验 | Protein kinase assays : Protein kinase assays are either done in-house by ELISA-based assay methods (Kit, KDR, PDGFRα, and PDGFRβ) or by a radiometric method. In-house ELISA assays used poly(Glu:Tyr) as the substrate bound to the surface of 96-well assay plates; phosphorylation is then detected using an antiphosphotyrosine antibody conjugated to HRP. The bound antibody is then quantitated using ABTS as the peroxidase substrate by measuring the absorbance at 405/490 nm. All assays uses purified recombinant kinase catalytic domains that are either expressed in insect cells or in bacteria. The Kit and EGFR protein used for in-house assays are prepared internally; other enzymes are obtained. Recombinant Kit protein is expressed as an NH2-terminal glutathione S-transferase fusion protein in insect cells and is initially purified as a nonphosphorylated (nonactivated) enzyme with a relatively high Km for ATP (400 μM). In some assays, an activated (tyrosine phosphorylated) form of the enzyme is prepared by incubation with 1 mM ATP for 1 hour at 30 °C. The phosphorylated protein is then passed through a desalting column to remove the majority of the ATP and stored at ?80 °C in buffer containing 50% glycerol. The resultant preparation has a considerably higher specific activity and a lower Km for ATP (25 μM) than the initial nonphosphorylated preparation. The inhibition of Kit autophosphorylation by OSI-930 is assayed by incubation of the nonphosphorylated enzyme at 30 °C in the presence of 200 μM ATP and various concentrations of OSI-930. The reaction is stopped by removal of aliquots into SDS-PAGE sample buffer followed by heating to 100 °C for 5 minutes. The degree of phosphorylation of Kit is then determined by immunoblotting for both total Kit and phosphorylated Kit. |
| 体外活性 | In guinea pigs, oral administration of MK-0752 (10-30 mg/kg) resulted in a dose-dependent reduction of Aβ40 in the plasma, brain, and cerebrospinal fluid. Similarly, in monkeys, MK-0752 (240 mg/kg) was capable of reducing the production of Aβ in the brain. |
| 体内活性 | In human SH-SY5Y cells, MK-0752 significantly reduces Aβ40 in a dose-dependent manner with an IC50 of 5 nM. |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 89 mg/mL (200.94 mM)
Ethanol : 45 mg/mL (101.6 mM)
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| 关键字 | Aβ40 | inhibit | barrier | γ-secretase | blood-brain | Inhibitor | MK 0752 | CNS | MK0752 | MK-0752 | Gamma secretase |
| 相关产品 | Anle138b | Notoginsenoside R1 | Geniposide | Deferoxamine Mesylate | Valproic acid sodium salt | Tramiprosate | Dihydroergocristine mesylate | Rutin | Valproic Acid | CB-103 | Carvacrol | Methyl tridecanoate |
| 相关库 | 经典已知活性库 | 神经退行性疾病化合物库 | 儿童药物库 | ReFRAME 相关化合物库 | 抗癌临床化合物库 | 药物功能重定位化合物库 | 抑制剂库 | 已知活性化合物库 | 抗癌药物库 | 抗癌活性化合物库 |
United States
