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Midostaurin(PKC412)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Midostaurin(PKC412)图片
CAS NO:120685-11-2
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
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.
理化性质和储存条件
Molecular Weight (MW)570.64
FormulaC35H30N4O4
CAS No.120685-11-2
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO:>50 mg/mL
Water: <1 mg/mL
Ethanol: <1 mg/mL
Other infoChemical 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
InChi Key: BMGQWWVMWDBQGC-IIFHNQTCSA-N
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
SMILES Code: 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
Synonymstrade name: Rydapt; PKC-412; CGP41251; PKC412; CGP 41251; PKC 412; PKC412A; PKC-412A; PKC 412A; CGP-41251;
实验参考方法
In Vitro

In vitro activity: 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.


Kinase Assay: 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.


Cell Assay: Midostaurin shows reversible inhibition of intracellular PKC activity with IC50 value of 0.5μM. Besides PKC, midostaurin inhibits the autophosphorylation of the receptors for PDGF, VEGF and stem cell factor with IC50 values of 80nM, 1μM and 30nM, respectively. Midostaurin also inhibits the FGF-induced c-fos transcription and MAPK activation. Moreover, midostaurin suppresses cell growth of different cell lines through inducing cell cycle arrest in G2/M and inducing apoptosis. 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 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.

In VivoMidostaurin(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.
Animal modelColo 205 colorectal tumors xenograft
Formulation & DosageDissolved in sterile water; 50, 200 mg/kg, once daily; p.o
ReferencesPharmacol Ther. 1999 May-Jun;82(2-3):293-301; Jpn J Pharmacol. 1996 Jan;70(1):65-72.