product name Staurosporine
Description: Staurosporine, also known as antibiotic AM-2282, CGP 41251 or STS, is a potent and non-selective PKC inhibitor for PKCα, PKCγ and PKCη with IC50 of 2 nM, 5 nM and 4 nM, it less potent to PKCδ (20 nM), PKCε (73 nM) and has little active to PKCζ (1086 nM) in cell-free assays. It also shows inhibitory activities on other kinases, such as PKA, PKG, S6K, CaMKII, etc. Staurosporine is a natural product originally isolated in 1977 from the bacterium Streptomyces staurosporeus with anti-fungal to anti-hypertensive.
References: Biochem Biophys Res Commun. 1986 Mar 13;135(2):397-402; Eur J Biochem. 1995 Nov 15;234(1):317-22.
466.53
Formula
C28H26N4O3
CAS No.
62996-74-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 4 mg/mL (8.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
CGP 41251
other peoduct :
| In Vitro |
In vitro activity: Staurosporine, a microbial alkaloid, significantly inhibits protein kinase C from rat brain with IC50 of 2.7 nM. Staurosporine displays strong inhibitory effect against HeLa S3 cells with IC50 of 4 NM. Staurosporine also inhibits a variety of other protein kinases, including PKA, PKG, phosphorylase kinase, S6 kinase, Myosin light chain kinase (MLCK), CAM PKII, cdc2, v-Src, Lyn, c-Fgr, and Syk with IC50 of 15 nM, 18 nM, 3 nM, 5 nM, 21 nM, 20 nM, 9 nM, 6 nM, 20 nM, 2 nM, and 16 nM, respectively. Staurosporine (1 μM) induces >90% apoptosis in PC12 cells. Consistently, Staurosporine treatment induces a rapid and prolonged elevation of intracellular free calcium levels [Ca2+]i, accumulation of mitochondrial reactive oxygen species (ROS), and subsequent mitochondrial dysfunction. The apoptosis of MCF7 cells induced by Staurosporine can be enhanced by the expression of functional caspase-3 via caspase-8 activation and Bid cleavage. Staurosporine treatment at 1 μM only partially inhibits IL-3-stimulated Bcl2 phosphorylation but completely blocks PKC-mediated Bcl2 phosphorylation. Staurosporine induces apoptosis of human foreskin fibroblasts AG-1518, depending on the lysosomal cathepsins D mediated cytochrome c release and caspase activation. In addition to activating the classical mitochondrial apoptosis pathway, Staurosporine triggers a novel intrinsic apoptosis pathway, relying on the activation of caspase-9 in the absence of Apaf-1. Kinase Assay: Protein kinase C is assayed in a reaction mixture (0.25 mL) containing 5 μmol of Tris/HCl, pH 7.5, 2.5 μmol of magnesium acetate, 50 μg of histone II S, 20 μg of phosphatidylserine, 0.88 μg of diolein, 125 nmol of CaCl2, 1.25 nmol of [γ-32]ATP (5-10 × 104 cpm/nmol) and 5 μg of partially purified enzyme. The binding of [3H]PDBu to protein kinase C is determined: Reaction mixture (200 μL contained 4 μmo1 of Tris/malate, pH 6.8, 20 μmol of KCl, 30 nmol of CaC12, 20 μg of phosphatidylserine, 5 μg of partially purified protein kinase C, 0.5% (final concentration) of DMSO,10 pmol of [3H]PDBu (l-3 × 104 cpm/pmol) and 10 μL of various amounts of Staurosporine. Cell Assay: Cells are exposed to Staurosporine for ~32 hours. Cells are fixed in 4% paraformaldehyde and stained with the DNA-binding dye Hoechst 33342. Cells are visualized under epifluorescence illumination, and the percentage of apoptotic cells (cells with condensed and fragmented DNA) is determined. |
|---|---|
| In Vivo | In the gerbil and rat ischemia models, Staurosporine pretreatment (0.1-10 ng) before ischemia prevents neuronal damage in a dose-dependent manner, suggesting the involvement of PKC in CAl pyramidal cell death after ischemia. |
| Animal model | Male Mongolian gerbils or male Wistar rats subjected to transient ischemia |
| Formulation & Dosage | Dissolved in DMSO and diluted in saline; 10 ng; Stereotaxically administered into the bilateral CAl subfield of the hippocampus |
| References | Biochem Biophys Res Commun. 1986 Mar 13;135(2):397-402; Eur J Biochem. 1995 Nov 15;234(1):317-22; J Cereb Blood Flow Metab. 1990 Sep;10(5):646-53. |
