| 名称 | Midostaurin |
| 描述 | Midostaurin (PKC412) is a multi-targeted tyrosine kinase inhibitor with antitumor activity, exhibiting IC50 values ranging from 22 to 500 nM against PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ, and VEGFR1/2. Midostaurin is indicated for the treatment of acute myeloid leukemia (AML) and systemic mastocytosis (SM). |
| 细胞实验 | Each well is added with 5 mM WST-1 and 0.2 mM 1-methoxy PMS and the absorbance at 450 nm is measured by a Microplate Reader.(Only for Reference) |
| 激酶实验 | Cells are plated overnight and treated with 100 nM AZD3965 or vehicle for 24 hours. The cells are then washed, once in PBS and twice with lysis buffer (50 mM Mops, 100 mM KCl, 5 mM MgCl2, 1 mM EDTA, 0.1 mM DTT, 1 mM PMSF supplemented with 1× mini complete protease inhibitor cocktail tablets. The cells are harvested by scraping and centrifugation, and the pellet snap frozen without buffer in liquid nitrogen. Frozen aliquots of cells are thawed on ice and re-suspended in lysis buffer. Cells are lysed by 3 rounds of freezing in liquid nitrogen and thawing at 37°C for 2 minutes each. Lysates are subsequently centrifuged (13000 g, 10min, 4°C) until clear and then stored on ice. Enzyme activity in the cell lysates is determined using a micro-plate reader to measure either production or depletion of NADH/NADPH, through its absorbance at 340/10 nm, occurring as a result of direct or coupled enzyme reactions. The 96 well plates used for the assays are pre-heated to 37°C for 10 minutes prior to starting reactions, initiated by the addition of 5 μL cell lysate to 95 μL of reaction buffer (50 mM Mops pH 7.4, 100 mM KCl, 5 mM free magnesium). The standard reaction buffer is supplemented to assay the kinetics of the different enzymes. Absorbance values for controls are subtracted from absorbance of corresponding reactions. Graphpad prism 6 is used to plot V0 values against substrate concentration and determine Vmax and Km values. The Vmax is then normalised to the protein concentration in the cell lysate[1]. |
| 体外活性 | 方法：肥大细胞白血病细胞系 HMC-1.1，加入 Midostaurin（1 μM），处理 24-48 小时，TUNEL 染色检测细胞凋亡情况。
结果：Midostaurin 能显著诱导细胞凋亡。[1]
方法： K562-FLT3 细胞（在 K562 细胞中过表达 FLT3）加入浓度梯度 Midostaurin （ 0.001 - 10 μM）处理，处理 72 小时。
结果：Midostaurin 对 K562-FLT3 细胞有显著的抑制作用。[2] |
| 体内活性 | 方法：将 K562-FLT3 细胞皮下接种于免疫缺陷小鼠。待肿瘤可触及后，随机分组开始给药。Midostaurin 50 mg/kg，每日一次，口服灌胃。 Imatinib 50 mg/kg，每日两次，口服灌胃。联合治疗组同时给予上述剂量的 Midostaurin 和 Imatinib。
结果： 联合治疗组小鼠的肿瘤生长被显著抑制。[2] |
| 存储条件 | 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 : 5 mg/mL (8.76 mM), Sonication is recommended.
DMSO : 247.5 mg/mL (433.72 mM), Sonication is recommended.
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| 关键字 | VEGFR | Vascular endothelial growth factor receptor | SCFR | Protein kinase C | PPK | PKCγ | PKCβ2 | PKCβ1 | PKCα | PKC-412 | PKC 412 | PKC | NOS | NO Synthase | Nitric oxide synthases | Midostaurin | Inhibitor | inhibit | c-Kit | CGP-41251 | CGP41251 | CGP-41231 | CGP 41231 | CD117 | Apoptosis |
| 相关产品 | Formamide | Urea | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Sildenafil citrate | Citric Acid Triammonium | Stavudine | Gluconate Calcium | Tamoxifen |
| 相关库 | 经典已知活性库 | 抗癌活性化合物库 | 激酶抑制剂库 | 临床失败化合物库 | 抗病毒库 | TGF-β/Smad靶点化合物库 | 免疫/炎症分子化合物库 | 膜蛋白靶向化合物库 | 药物功能重定位化合物库 | 酪氨酸激酶分子库 | 抗癌临床化合物库 | 抗癌药物库 |