Midostaurin
Midostaurin structure
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Common Name | Midostaurin | ||
|---|---|---|---|---|
| CAS Number | 120685-11-2 | Molecular Weight | 570.637 | |
| Density | 1.5±0.1 g/cm3 | Boiling Point | N/A | |
| Molecular Formula | C35H30N4O4 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of MidostaurinMidostaurin (CGP41231; PKC412) is a multi-targeted protein kinase inhibitor which inhibits PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC50 ranging from 16-500 nM. |
| Name | midostaurin |
|---|---|
| Synonym | More Synonyms |
| Description | Midostaurin (CGP41231; PKC412) is a multi-targeted protein kinase inhibitor which inhibits PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC50 ranging from 16-500 nM. |
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| Related Catalog | |
| Target |
nPKC-η:16 nM (IC50) cPKC-α:22 nM (IC50) cPKC-γ:24 nM (IC50) cPKC-β1:30 nM (IC50) cPKC-β2:31 nM (IC50) nPKC-δ:33 nM (IC50) nPKC-ε:1250 nM (IC50) aPKC-ζ:465000 nM (IC50) PPK:38 nM (IC50) KDR:86 nM (IC50) c-Syk:95 nM (IC50) cdk1/cycB:570 nM (IC50) Protein kinase A:570 nM (IC50) c-Fgr:790 nM (IC50) c-Src:800 nM (IC50) Flt-1:912 nM (IC50) EGF-R:1100 nM (IC50) Myosin-light chain kinase:1900 nM (IC50) Flk-1:3900 nM (IC50) c-Lyn:4300 nM (IC50) P70S6 kinase:5000 nM (IC50) CSK:8000 nM (IC50) |
| 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) with ponatinib induced substantial inhibition of KIT-, Lyn-, and STAT5 activity, but did not suppress Btk in HMC-1 cells and primary neoplastic mast cells[2]. 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[3]. |
| In Vivo | Midostaurin (PKC412) strongly inhibits retinal neovascularization as well as laser-induced choroidal neovascularization in murine models[1]. Midostaurin (PKC412) (25 mg/kg, i.p.) protects mouse livers of the K18 Arg90Cys-overexpressing transgenic mice from Fas-induced apoptosis[4]. |
| Cell Assay | 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 Admin | 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]. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Molecular Formula | C35H30N4O4 |
| Molecular Weight | 570.637 |
| Exact Mass | 570.226685 |
| PSA | 77.73000 |
| LogP | 5.27 |
| Index of Refraction | 1.770 |
| Storage condition | -20℃ |
| Hazard Codes | T: Toxic; |
|---|
| 4'-N-benzoylstaurosporine |
| Benzamide, N-[(6S,7R,8R,10R)-7,8,9,10,17,18-hexahydro-7-methoxy-6-methyl-16-oxo-6,10-epoxy-6H,16H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-8-yl]-N-methyl- |
| PKC 412,[9S-(9α,10β,11β,13α)]-N-(2,3,10,11,12,13-Hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-11-yl)-N-methylbenzamide |
| Cgp 41 251 |
| Midostaurin |
| 4'-N-benzoyl staurosprine |
| Benzoylstaurosporine |
| N-[(2S,3R,4R,6R)-3-Methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.1.0.0.0.0.0]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide |
| PKC412 |
| PKC-412 |