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Purity: ≥98%
Midostaurin (formerly also known as PKC-412; CGP41251; PKC412; CGP 41251; PKC 412; PKC412A; trade name: Rydapt), a synthetic indolocarbazole compound, is a multi-targeted kinase inhibitor with potential with potential antiangiogenic and antineoplastic activities. It inhibits multiple kinases such as PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC50s ranging from 80-500 nM. In April 2018, Midostaurin was approved by FDA to treat acute myeloid leukemia. Midostaurin is a synthetic indolocarbazole multikinase inhibitor with potential antiangiogenic and antineoplastic activities. Midostaurin inhibits PKCalpha, VEGFR2, c-kit, PDGFR and FLT3, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors.
| ln Vitro |
In vitro, midostaurin (PKC412) reverses Pgp-mediated multidrug resistance in tumor cells and demonstrates wide antiproliferative efficacy against a variety of tumor and normal cell types. A dose-dependent increase in the G2/M phase of the cell cycle, as well as increased polyploidy, apoptosis, and greater sensitivity to ionizing radiation, are the outcomes of cells being exposed to midostaurin (PKC412) [1]. In HMC-1 cells and primary tumor mast cells, midostaurin (PKC412) significantly inhibits KIT-, Lyn-, and STAT5 activities, but not Btk [3]. In hematopoietic Ba/F3 cells, midostaurin (PKC412) inhibits EN fusion tyrosine kinase. EN phosphorylation in M0-91 and IMS-M2 cells is strongly inhibited by midostaurin (PKC412) in a dose-dependent manner [4].
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| ln Vivo |
In mouse models, midostaurin (PKC412) significantly inhibits both laser-induced choroidal neovascularization and retinal neovascularization [1]. For K18 Arg90Cys-overexpressing transgenic mice, midostaurin (PKC412) (25 mg/kg, i.p.) prevents Fas-induced apoptosis in the livers [5].
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| 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]. 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. [5]. 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. [6]. 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 |
| Molecular Formula |
C35H30N4O4
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|---|---|
| Molecular Weight |
570.64
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| CAS # |
120685-11-2
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| Related CAS # |
Midostaurin-d5
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| SMILES |
C[C@@]12[C@H](OC)[C@H](N(C(C3=CC=CC=C3)=O)C)C[C@H](N4C5=CC=CC=C5C6=C7C(CNC7=O)=C8C9=CC=CC=C9N2C8=C64)O1
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| InChi Key |
BMGQWWVMWDBQGC-IIFHNQTCSA-N
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| InChi Code |
InChI=1S/C35H30N4O4/c1-35-32(42-3)25(37(2)34(41)19-11-5-4-6-12-19)17-26(43-35)38-23-15-9-7-13-20(23)28-29-22(18-36-33(29)40)27-21-14-8-10-16-24(21)39(35)31(27)30(28)38/h4-16,25-26,32H,17-18H2,1-3H3,(H,36,40)/t25-,26-,32-,35+/m1/s1
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| Chemical Name |
N-((5R,7R,8R,9S)-8-methoxy-9-methyl-16-oxo-6,7,8,9,15,16-hexahydro-5H,14H-17-oxa-4b,9a,15-triaza-5,9-methanodibenzo[b,h]cyclonona[jkl]cyclopenta[e]-as-indacen-7-yl)-N-methylbenzamide
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| Synonyms |
trade name: Rydapt; PKC-412; CGP41251; PKC412; CGP 41251; PKC 412; PKC412A; PKC-412A; PKC 412A; CGP-41251;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7524 mL | 8.7621 mL | 17.5242 mL | |
| 5 mM | 0.3505 mL | 1.7524 mL | 3.5048 mL | |
| 10 mM | 0.1752 mL | 0.8762 mL | 1.7524 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 PKC412 treatment mitigates abnormal K18 R90C punctate staining, normalizes keratin filament organization and protects against Fas-induced apoptosis in A549 cells.
The effect of phosphorylation status on the association of NMHC-IIA with K8/K18 in cultured cells and in mouse liver.Hepatology.2015 Dec;62(6):1858-69. |
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 PKC412 treatment reduces abnormal K18 R90C punctate staining and protects against Fas-induced liver injury in K18 R90C transgenic mice.Hepatology.2015 Dec;62(6):1858-69. |
 NMHC-IIA mediates the PKC412-modulated normalization of K18 R90C disorganization.
NMHC-IIA expression is required for PKC412-mediated filament normalization.Hepatology.2015 Dec;62(6):1858-69. |
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