Midostaurin (PKC412)

For research use only. Not for use in humans.

目录号:S8064 别名: CGP 41251 中文名称:米哚妥林

Midostaurin (PKC412) Chemical Structure

CAS No. 120685-11-2

Midostaurin (pkc412, CGP 41251) 是一种多靶点激酶抑制剂,作用于PKCα/β/γSykFlk-1AktPKAc-Kitc-Fgrc-SrcFLT3PDFRβVEGFR1/2IC50为80-500 nM。

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客户使用Selleck生产的Midostaurin (PKC412)发表文献24篇:

产品安全说明书

PKC抑制剂选择性比较

生物活性

产品描述 Midostaurin (pkc412, CGP 41251) 是一种多靶点激酶抑制剂,作用于PKCα/β/γSykFlk-1AktPKAc-Kitc-Fgrc-SrcFLT3PDFRβVEGFR1/2IC50为80-500 nM。
靶点
PKCα [1]
(Cell-free assay)
PKCγ [1]
(Cell-free assay)
PKCβ1 [1]
(Cell-free assay)
PKCβ2 [1]
(Cell-free assay)
PPK [1]
(Cell-free assay)
22 nM 24 nM 30 nM 31 nM 38 nM
体外研究

Midostaurin(pkc412)是一种广谱的蛋白激酶抑制剂。Midostaurin(pkc412)强烈与常规PKC-α, -β 和 -γ, PDGFRβ, VEGF-R2, VEGF-R1,及CDK 1-cyclin B复合物的ATP结合位点相互作用。Midostaurin(pkc412)在相似的亚微摩尔浓度时,在体外抑制多种人类和动物细胞系的生长。Midostaurin(pkc412) 在体外也有效抑制胶质母细胞瘤增殖,且诱导细胞在G2/M期累积,并形成巨核,具有广泛的碎片和凋亡小体。Midostaurin(pkc412)在体外能够逆转肿瘤细胞中p-糖蛋白介导的多药耐药性。[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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MV4-11 MYXDfZRwfG:6aXPpeJkh[XO|YYm= MXO3NkBpenN? NUfIfHZWS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVVZ2LUGxJINmdGy|IHHmeIVzKDd{IHjyd{BjgSClZXzsJJRqfGW{LXLseYUh[XO|YYmsJGlEPTBiPTCwMlAyOiEQvF2u MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTZ3NESwPEc,OTl4NUS0NFg9N2F-
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MHH-CALL-2 NEHhbphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXLJcohq[mm2aX;uJI9nKGi3bXHuJG1JUC2FQVzMMVIh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDFyLkCxOlkh|ryPLh?= M1fDeFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFYxQDV|Mz:nQnNCVkeHUkyvZV4>
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-TYR / p-STAT5 / STAT5 / p-S6 / S6 / p-MAPK / MAPK / p-AKT / AKT ; 

PubMed: 28881711     


Effect of midostaurin and PRT062607 on TEL-SYK phosphorylation and phosphorylation of downstream effectors following 2 hr of treatment. For the experiment analyzing effects of midostaurin and PRT062607 on phosphorylation of TEL-SYK, SYK immunoprecipitation was carried out prior to immunoblotting with a PTYR (4G10) antibody. Immunoblotting was performed for the experiment analyzing effects of midostaurin and PRT062607 on signaling molecules downstream of TEL-SYK. Relative densitometry readings for pMAPK/total MAPK (normalized to control lane) are as follows: 0 nM midostaurin=1.0, 10 nM midostaurin=0.93, 100 nM midostaurin=0.41, 1000 nM midostaurin=0.04, 0 nM PRT062607=1.0, 10 nM PRT062607=0.72, 100 nM PRT062607=0.37, 1000 nM PRT062607=0.07. 

PKCα / PKCβ1 / PKCβ2 / PKCγ / PKCη / p-PKC / p-Bad / Bad / p-Bcl2 / Bcl-2 / p-p65 / p65; 

PubMed: 30584254     


The indicated PKC isoforms were up-regulated in the resistant BL cells, leading to elevated levels of PKC phosphorylation and the activation of downstream anti-apoptotic proteins.

28881711 30584254
体内研究 Midostaurin(pkc412) 除了直接抑制肿瘤细胞增殖(通过作用于PKCs),还通过抑制肿瘤血管生成(通过作用于VEGF受体酪氨酸激酶)来抑制肿瘤的生长。Midostaurin(pkc412)与细胞毒性剂,包括Doxorubicin, Cyclophosphamide, Cisplatin 和 Gemcitabine协同作用,产生的抗血管生成作用可能有助于抗转移和广泛的抗肿瘤活性。Midostaurin(pkc412)口服给药,最大耐受剂量为300 mg/kg以上。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

细胞实验:[2]
- 合并
  • Cell lines: A549, NCI-H520
  • Concentrations: ~1.0 μM
  • Incubation Time: 24-72 小时
  • Method: 每孔加入5 mM WST-1和0.2 mM 1-甲氧基PMS,然后使用酶标仪在450nm处测量吸光度。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: Colo 205 结肠移植瘤
  • Dosages: 50 mg/kg, 200 mg/kg, 每天一次
  • Administration: 口服处理
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 100 mg/mL (175.24 mM)
Water Insoluble
Ethanol ''''''20 mg/mL warmed
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
5% DMSO+45% PEG 300+ddH2O
4mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 570.64
化学式

C35H30N4O4

CAS号 120685-11-2
储存条件 粉状
溶于溶剂
别名 CGP 41251

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03951961 Recruiting Drug: Midostaurin Acute Myeloid Leukemia Adult Sebastian Scholl PD Dr. med.|Ludwig-Maximilians - University of Munich|University of Jena March 20 2020 Phase 2
NCT04097470 Recruiting Drug: Decitabine|Drug: Midostaurin AML/MDS Stichting Hemato-Oncologie voor Volwassenen Nederland|Swiss Group for Clinical Cancer Research December 5 2019 Phase 2

技术支持

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操作手册

如果有其他问题,请给我们留言。

  • * 必填项

PKC Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID