Product Introduction
Bioactivity


英文名: Midostaurin

描述: Midostaurin (PKC412) 是一种多靶点蛋白激酶抑制剂，有抗肿瘤活性，对 PKCα/β/γ、Syk、Flk-1、Akt、PKA、c-Kit、c-Fgr、c-Src、FLT3、PDFRβ和VEGFR1/2的IC50值范围为 22 到500 nM 之间。

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: Midostaurin(pkc412) is a broad spectrum protein kinase inhibitor. Midostaurin(pkc412) interacts strongly with ATP binding sites of the conventional PKC-α, -β and -γ, PDGFRβ, VEGF-R2, VEGF-R1 and the cyclin-dependant kinase 1-cyclin B complex. Midostaurin(pkc412) inhibits the growth of various human and animal cell lines in vitro at similar submicromolar concentrations. Midostaurin(pkc412) also effectively inhibits the in vitro proliferation of glioblastoma and induced the accumulation of cells in G2/M and formation of giant nuclei with extensive fragmentation and apoptotic bodies. Midostaurin(pkc412) is able to reverse the p-glycoprotein-mediated multidrug resistance of tumor cells in vitro. [1]

体内活性: Midostaurin(pkc412) may suppress tumor growth by inhibiting tumor angiogenesis (via its effects on the VEGF receptor tyrosine kinases) in addition to directly inhibiting tumor cell proliferation (via its effects on PKCs). This anti-angiogenic action may contribute to the antimetastatic and broad antitumor activity displayed by midostaurin(pkc412), as well as the synergy with cytotoxic agents, including doxorubicin, cyclophosphamide, cisplatin and gemcitabine. When given orally, the maximally tolerated dose for midostaurin(pkc412) is >300 mg/kg. [1]

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 8.6 mg/mL (15 mM)


关键字: CGP-41251 | Nitric oxide synthases | SCFR | inhibit | CGP-41231 | Protein kinase C | Inhibitor | Apoptosis | NO Synthase | CD117 | Midostaurin | c-Kit | VEGFR | PKC-412 | NOS | PKC 412 | CGP 41231 | CGP41251 | Vascular endothelial growth factor receptor | PKC

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相关库: Drug Repurposing Compound Library | FDA-Approved Kinase Inhibitor Library | Anti-Cancer Drug Library | Kinase Inhibitor Library | Inhibitor Library | Anti-Cancer Clinical Compound Library | Anti-Cancer Approved Drug Library | Anti-Cancer Active Compound Library | EMA Approved Drug Library | TGF-beta/Smad Compound Library