| 名稱(chēng) | 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). |
| 細(xì)胞實(shí)驗(yàn) | 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) |
| 激酶實(shí)驗(yàn) | 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]. |
| 體外活性 | 方法：肥大細(xì)胞白血病細(xì)胞系 HMC-1.1，加入 Midostaurin（1 μM），處理 24-48 小時(shí)，TUNEL 染色檢測(cè)細(xì)胞凋亡情況。
結(jié)果：Midostaurin 能顯著誘導(dǎo)細(xì)胞凋亡。[1]
方法： K562-FLT3 細(xì)胞（在 K562 細(xì)胞中過(guò)表達(dá) FLT3）加入濃度梯度 Midostaurin （ 0.001 - 10 μM）處理，處理 72 小時(shí)。
結(jié)果：Midostaurin 對(duì) K562-FLT3 細(xì)胞有顯著的抑制作用。[2] |
| 體內(nèi)活性 | 方法：將 K562-FLT3 細(xì)胞皮下接種于免疫缺陷小鼠。待腫瘤可觸及后，隨機(jī)分組開(kāi)始給藥。Midostaurin 50 mg/kg，每日一次，口服灌胃。 Imatinib 50 mg/kg，每日兩次，口服灌胃。聯(lián)合治療組同時(shí)給予上述劑量的 Midostaurin 和 Imatinib。
結(jié)果： 聯(lián)合治療組小鼠的腫瘤生長(zhǎng)被顯著抑制。[2] |
| 存儲(chǔ)條件 | Keep away from moisture,
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.
|
| 關(guān)鍵字 | 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 |
| 相關(guān)產(chǎn)品 | Urea | Formamide | Dimethyl phthalate | Aceglutamide | Alginic acid | Dextran sulfate sodium salt (MW 5000) | Metronidazole | Sildenafil citrate | Stavudine | Gluconate Calcium | Tamoxifen | Adenosine |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | 臨床失敗化合物庫(kù) | EMA 上市藥物庫(kù) | FDA 上市藥物庫(kù) | TGF-β/Smad靶點(diǎn)化合物庫(kù) | 膜蛋白靶向化合物庫(kù) | 藥物功能重定位化合物庫(kù) | 酪氨酸激酶分子庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |