product name Midostaurin (PKC412)
Description: Midostaurin (also known as PKC-412, PKC-412A and 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. 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.
References: Pharmacol Ther. 1999 May-Jun;82(2-3):293-301; Jpn J Pharmacol. 1996 Jan;70(1):65-72.
412.48
Formula
C25H24N4O2
CAS No.
133052-90-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 82 mg/mL (198.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
GO 6850 , Bisindolylmaleimide I
other peoduct :
| 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: 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. |
|---|---|
| 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. |
| Animal model | Colo 205 colorectal tumors xenograft |
| Formulation & Dosage | Dissolved in sterile water; 50, 200 mg/kg, once daily; p.o |
| References | Pharmacol Ther. 1999 May-Jun;82(2-3):293-301; Jpn J Pharmacol. 1996 Jan;70(1):65-72. |
