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Midostaurin

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Chemical Structure| 120685-11-2 同义名 : 苯甲酰基十字孢碱 ;PKC412;CGP 41251;Rydapt;PKC412A;CGP 41231;N-Benzoylstaurosporine
CAS号 : 120685-11-2
货号 : A297057
分子式 : C35H30N4O4
纯度 : 99%
分子量 : 570.637
MDL号 : MFCD00871372
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(87.62 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5% DMSO+45% PEG 300+water 4 mg/mL

生物活性
靶点

  • PKCη

    PKCη, IC50:160 nM

  • PKCβ

    PKCβ2, IC50:31 nM

    PKCβ1, IC50:30 nM

  • PKCγ

    PKCγ, IC50:24 nM

  • PKCε

    PKCε, IC50:1.25 μM
描述 PKC412, a prototype kinase inhibitor, was originally identified as an inhibitor preferentially against PKC (protein kinase C), with IC50 values of 22 nM, 24 nM, 30 nM, 31 nM, 160 nM and 330 nM for PKCα, PKCγ, PKCβ1, PKCβ2, PKCη and PKCδ, respectively, and subsequently shown as a multi-target inhibitor with IC50 values of 38 nM, 86 nM, 95 nM, 390 nM, 570 nM, 570 nM, 790 nM, 800 nM, 912 nM, 1.1 μM, 1.25 μM and 1.9 μM for PPK, KDR, c-Syk, Flk1, CDK1/CyclinB, PKA, c-FGR, c-Src, FLT1, EGFR, PKCε, Myosin-light chain kinase (measured by recombinant enzymatic activity)[1]. PKC412 showed anti-proliferatively active in T-24, HL-60 and bovine corneal endothelial cell lines with IC50 values of 0.029μM, 0.13μM and 0.022μM, respectively. In the presence of PKC412 with concentration ranged from 0.1μM to 10μM, the release of H202 induced by PMA, the activator of PKC, in monocytes was decreased in a concentration-dependent manner. PKC412 showed more potent anti-tumor activity than staurosporine against T-24 bladder carcinoma xenografts in athymic nude mice[2]. For recently it was found that PKC412 was a potent inhibitor of FLT3 tyrosine kinase and has activity against mutant forms of KIT proto-oncogene receptor tyrosine kinase, which drived advanced systemic mastocytosis. PKC412 was in development in approval for treating acute myeloid leukemia and advanced systemic mastocytosis[3].
作用机制 PKC412 is a derivative of staurosporine, which is an ATP-competitive inhibitor of PKC[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A172 cell Growth inhibition assay Inhibition of human A172 cell growth in a cell viability assay, IC50=0.2915 μM SANGER
A204 cell Growth inhibition assay Inhibition of human A204 cell growth in a cell viability assay, IC50=0.10052 μM SANGER
A375 cells Cytotoxicity assay 72 h Toxicity against human A375 cells after 72 hrs by cell titer-blue assay, IC50=0.18 μM 19654408
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.75mL

0.35mL

0.18mL

8.76mL

1.75mL

0.88mL

17.52mL

3.50mL

1.75mL
参考文献

[1]Fabbro D, Buchdunger E, et al. Inhibitors of protein kinases: CGP 41251, a protein kinase inhibitor with potential as an anticancer agent. Pharmacol Ther. 1999 May-Jun;82(2-3):293-301.

[2]Meyer T, Regenass U, et al. RETRACTED ARTICLEA derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and in vitro anti-proliferative as well as in vivo anti-tumor activity. Int J Cancer. 1989 May 15;43(5):851-6.

[3]Gotlib J, Kluin-Nelemans HC, et al. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41.

[4]Pharmacodynamic studies of midostaurin

[5]PK parameters of PKC412