| CAS |
120685-11-2 |
| Chinese Name |
米哚妥林 |
| English Name |
Midostaurin |
| Synonyms |
米哚妥林;NCGC00188654;CGP41251 |
| Molecular Formula |
C35H30N4O4 |
| Molecular Weight |
570.64 |
| Solubility |
Soluble in DMSO |
| Purity |
≥98% |
| Appearance |
White to yellow Solid |
| Storage |
Powder:-20℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD00871372 |
| SMILES |
O=C(C1=CC=CC=C1)N(C)[C@H]2[C@@H](OC)[C@@]3(C)N(C4=C5C=CC=C4)C6=C5C7=C(C(NC7)=O)C8=C6N(C9=CC=CC=C98)[C@@](O3)([H])C2 |
| Target Point |
PKC;Syk;Flk-1;Akt;PKA;c-Kit |
| Passage |
TGF-beta/Smad;Epigenetics |
| Background |
Midostaurin is a multi-target kinase inhibitor that inhibits PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ, and VEGFR1/2. |
| In Vitro |
Midostaurin(PKC412)shows a broad antiproliferative activity against various tumor and normal cell lines in vitro，and is able to reverse the Pgp-mediated multidrug resistance of tumor cells in vitro. Exposure of cells to Midostaurin(PKC412)results in a dose-dependent increase in the G2/M phase of the cell cycle concomitant with increased polyploidy，apoptosis and enhanced sensitivity to ionizing radiation[1]. Midostaurin(PKC412)induces substantial inhibition of KIT-，Lyn-，and STAT5 activity，but does not suppress Btk in HMC-1 cells and primary neoplastic mast cells[3]. Midostaurin(PKC412)inhibits EN fusion tyrosine kinase in hematopoietic Ba/F3 cells. Midostaurin(PKC412)significantly inhibits EN phosphorylation in M0-91 and IMS-M2 cells in a dose-dependent manner[4]. |
| In Vivo |
Midostaurin(PKC412)strongly inhibits retinal neovascularization as well as laser-induced choroidal neovascularization in murine models[1]. |
| Cell Experiment |
Proliferation is determined by trypan blue dye exclusion test. Cells in suspension are seeded in six-well plates at a density of 1×105 cells/mL in the presence of different concentrations of PKC412 for 3 days. In control wells，DMSO instead of Midostaurin(PKC412)is added. After the treatment，10 μL of the cell suspension is mixed with 10 μL of 0.4% trypan blue，and alive cells are counted manually using a hemacytometer. Results are calculated as the percentage of the values measured when cells are grown in the absence of the reagent. All experiments are performed in triplicate[3]. |
| Animal Experiment |
K8-deficient，K18-deficient，and human K18 R90C-overexpressing mice with age of 6-8 weeks are used in the assay. Age and sex matched mice are treated with Midostaurin(25 mg/kg)，daily for 4 d or with an equal volume of DMSO as vehicle(both administered intraperitoneally). On day 5 post-treatment，apoptosis is induced by intraperitoneal injection of Fas ligand(Fas-L)(0.15 μg/g body weight). Mice are fasted overnight before Fas Ab injection，and 18 mice are used per DMSO or Midostaurin(PKC412)group for the Fas-treated mice while 6 mice are used per DMSO or Midostaurin(PKC412)group for the control non-Fas-treated mice. Mice are sacrificed by CO2 inhalation 6 h after Fas Ab injection. Blood is collected by intracardiac puncture，and livers are harvested for hematoxylin and eosin(HE)staining(after fixation in 10% formalin)or frozen in optimum cutting temperature compound for immunofluorescence staining[4]. |
| Data Literature Source |
[1]. Fabbro D，et al. PKC412--a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. 2000 Feb;15(1):17-28.
[2]. Fabbro D，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.
[3]. Huige Li，et al. Midostaurin upregulates eNOS gene expression and preserves eNOS function in the microcirculation of the mouse. Nitric Oxide. 2005 Jun;12(4):231-6.
[4]. Gleixner KV，et al. Synergistic growth-inhibitory effects of Midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V. Haematologica. 2013 Sep;98(9):1450-7. |
| Unit |
Bottle |
| Specification |
1mg 5mg |
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