DC Chemicals Limited
China
Product Name: PKC-412
Price: $650.0/100mg $1300.0/250mg $2700.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

Zhejiang Hangyu API Co., Ltd
China
Product Name: Midostaurin
Price: ￥Inquiry/1kg
Purity: 99.5%
Stocking Period: Inquiry
Contact: Vinnie

120685-11-2

120685-11-2 structure

120685-11-2 structure

Name: Midostaurin
Chemical Name: midostaurin
CAS Number: 120685-11-2
Molecular Formula: C₃₅H₃₀N₄O₄
Molecular Weight: 570.637
Catalog: Signaling Pathways Epigenetics PKC
Create Date: 2016-06-28 13:41:36
Modify Date: 2024-01-02 13:00:45
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.

Name	midostaurin
Synonyms	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

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.
Related Catalog	Signaling Pathways >> Epigenetics >> PKC Signaling Pathways >> TGF-beta/Smad >> PKC Research Areas >> Cancer
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	[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]. Gleixner KV, et al. Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V. Haematologica. 2013 Sep;98(9):1450-7. [3]. Chi HT, et al. ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412. Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):87-92. [4]. Kwan R, et al. PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding. Hepatology. 2015 Dec;62(6):1858-69. [5]. 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.

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;