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].
Midostaurin 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
A427 cell
Growth inhibition assay
Inhibition of human A427 cell growth in a cell viability assay, IC50=0.11918 μM
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