Midostaurin (PKC412)

For research use only.

Catalog No.S8064 Synonyms: CGP 41251

24 publications

Midostaurin (PKC412) Chemical Structure

CAS No. 120685-11-2

Midostaurin (pkc412, CGP 41251) is a multi-targeted kinase inhibitor, including PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC50 ranging from 80-500 nM.

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Selleck's Midostaurin (PKC412) has been cited by 24 publications

Purity & Quality Control

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Biological Activity

Description Midostaurin (pkc412, CGP 41251) is a multi-targeted kinase inhibitor, including PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC50 ranging from 80-500 nM.
Targets
PKCα [1]
(Cell-free assay)
PKCγ [1]
(Cell-free assay)
PKCβ1 [1]
(Cell-free assay)
PKCβ2 [1]
(Cell-free assay)
PPK [1]
(Cell-free assay)
22 nM 24 nM 30 nM 31 nM 38 nM
In vitro

Midostaurin(pkc412) is a broad spectrum protein kinase inhibitor. Midostaurin(pkc412) interacts strongly with ATP binding sites of the conventional PKC-α, -β and -γ, PDGFRβ, VEGF-R2, VEGF-R1 and the cyclin-dependant kinase 1-cyclin B complex. Midostaurin(pkc412) inhibits the growth of various human and animal cell lines in vitro at similar submicromolar concentrations. Midostaurin(pkc412) also effectively inhibits the in vitro proliferation of glioblastoma and induced the accumulation of cells in G2/M and formation of giant nuclei with extensive fragmentation and apoptotic bodies. Midostaurin(pkc412) is able to reverse the p-glycoprotein-mediated multidrug resistance of tumor cells in vitro. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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MV4-11 M13zTWN6fG:2b4jpZ4l1gSCjc4PhfS=> NVLIWpAzPzJiaILz M{\GdWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1XPC1zMTDj[YxteyCjZoTldkA4OiCqcoOgZpkh[2WubDD0bZRmei2kbIXlJIF{e2G7LDDJR|UxKD1iMD6wNVIh|ryPLh?= MnXLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl4NUS0NFgoRjF7NkW0OFA5RC:jPh?=
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FDC-P1 MlHUSpVv[3Srb36gZZN{[Xl? NUDYbXBIPDhiaILz MWHJcohq[mm2aX;uJI9nKGi3bXHuJGZOWyCneIDy[ZN{\WRiaX6g[5Jwf3SqIH\hZ5RweiCmZYDlcoRmdnRibX;1d4UhTkSFLWCxJINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiRl3TMY1m\GmjdHXkJINmdGxicILvcIln\XKjdHnvckBqdiCycnXz[Y5k\SCqdX3hckBEW0ZzIHHmeIVzKDR6IHjyd{BjgSC{ZYPhfpVzcW5iZInlJJJm\HWldHnvckBie3OjeTygTWM2OCB;IECuNVQzKM7:TT6= NV;GSYNxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCxOVY3QDlpPkKwNVU3Pjh7PD;hQi=>
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-TYR / p-STAT5 / STAT5 / p-S6 / S6 / p-MAPK / MAPK / p-AKT / AKT ; 

PubMed: 28881711     


Effect of midostaurin and PRT062607 on TEL-SYK phosphorylation and phosphorylation of downstream effectors following 2 hr of treatment. For the experiment analyzing effects of midostaurin and PRT062607 on phosphorylation of TEL-SYK, SYK immunoprecipitation was carried out prior to immunoblotting with a PTYR (4G10) antibody. Immunoblotting was performed for the experiment analyzing effects of midostaurin and PRT062607 on signaling molecules downstream of TEL-SYK. Relative densitometry readings for pMAPK/total MAPK (normalized to control lane) are as follows: 0 nM midostaurin=1.0, 10 nM midostaurin=0.93, 100 nM midostaurin=0.41, 1000 nM midostaurin=0.04, 0 nM PRT062607=1.0, 10 nM PRT062607=0.72, 100 nM PRT062607=0.37, 1000 nM PRT062607=0.07. 

PKCα / PKCβ1 / PKCβ2 / PKCγ / PKCη / p-PKC / p-Bad / Bad / p-Bcl2 / Bcl-2 / p-p65 / p65; 

PubMed: 30584254     


The indicated PKC isoforms were up-regulated in the resistant BL cells, leading to elevated levels of PKC phosphorylation and the activation of downstream anti-apoptotic proteins.

28881711 30584254
In vivo Midostaurin(pkc412) may suppress tumor growth by inhibiting tumor angiogenesis (via its effects on the VEGF receptor tyrosine kinases) in addition to directly inhibiting tumor cell proliferation (via its effects on PKCs). This anti-angiogenic action may contribute to the antimetastatic and broad antitumor activity displayed by midostaurin(pkc412), as well as the synergy with cytotoxic agents, including doxorubicin, cyclophosphamide, cisplatin and gemcitabine. When given orally, the maximally tolerated dose for midostaurin(pkc412) is >300 mg/kg. [1]

Protocol

Cell Research:[2]
- Collapse
  • Cell lines: A549, NCI-H520
  • Concentrations: ~1.0 μM
  • Incubation Time: 24-72 h
  • Method: Each well is added with 5 mM WST-1 and 0.2 mM 1-methoxy PMS and the absorbance at 450 nm is measured by a Microplate Reader.
    (Only for Reference)
Animal Research:[1]
- Collapse
  • Animal Models: Colo 205 colorectal tumors xenograft
  • Dosages: 50 mg/kg, 200 mg/kg, once daily
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (175.24 mM)
Water Insoluble
Ethanol ''''''20 mg/mL warmed
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+45% PEG 300+ddH2O
For best results, use promptly after mixing.
4mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 570.64
Formula

C35H30N4O4

CAS No. 120685-11-2
Storage powder
in solvent
Synonyms CGP 41251
Smiles CC12C(C(CC(O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)N(C)C(=O)C9=CC=CC=C9)OC

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Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
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To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03951961 Recruiting Drug: Midostaurin Acute Myeloid Leukemia Adult Sebastian Scholl PD Dr. med.|Ludwig-Maximilians - University of Munich|University of Jena March 20 2020 Phase 2
NCT04097470 Recruiting Drug: Decitabine|Drug: Midostaurin AML/MDS Stichting Hemato-Oncologie voor Volwassenen Nederland|Swiss Group for Clinical Cancer Research December 5 2019 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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PKC Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID