Staurosporine is a potent PKC inhibitor for PKCα/γ/η (IC50: 2/5/4 nM), less potent to PKCε (73 nM), PKCδ (20 nM) and little action to PKCζ (1086 nM).

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. [1] 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. [2] 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. [3] 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. [4] Staurosporine treatment at 1 μM only partially inhibits IL-3-stimulated Bcl2 phosphorylation but completely blocks PKC-mediated Bcl2 phosphorylation. [5] Staurosporine induces apoptosis of human foreskin fibroblasts AG-1518, depending on the lysosomal cathepsins D mediated cytochrome c release and caspase activation. [6] 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. [7]

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. [8]

Enzyme assay and binding 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.

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. (Only for Reference)

62996-74-1

C28H26N4O3

466.541

CGP 41251;Antibiotic AM-2282;星孢菌素;AM-2282;星形孢菌素;Staurosporine

[1]Tamaoki T, et al. Biochem Biophys Res Commun, 1986, 135(2), 397-402. [2]Meggio F, et al. Eur J Biochem, 1995, 234(1), 317-322. [3]Xiao Q, Ye T, Wang X, et al. A network pharmacology-based study on key pharmacological pathways and targets of Qi Fu Yin acting on Alzheimer's disease[J]. Experimental Gerontology. 2021: 111336. [4]Tang D, et al. J Biol Chem, 2000, 275(13), 9303-9307. [5]Deng X, et al. Proc Natl Acad Sci U S A, 2000, 97(4), 1578-1583. [6]Kruman I, et al. J Neurosci Res, 1998, 51(3), 293-308. [7]Yang J B, Song Y F, Liu Y, et al. UHPLC-QQQ-MS/MS assay for quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: Application to the standardization of TCMs with endogenous toxicity[J]. 2021

[1]Lü Z, Li X, Li K, et al. Nitazoxanide and related thiazolides induce cell death in cancer cells by targeting the 20S proteasome with novel binding modes. Biochemical Pharmacology. 2022: 114913. [2]Yang G, Wan P, Xiang Q, et al. E3 Ubiquitin Ligase ASB17 Promotes Apoptosis by Ubiquitylating and Degrading BCLW and MCL1. Biology-Basel. 2021, 10(3): 234. [3]Yang J B, Song Y F, Liu Y, et al. UHPLC-QQQ-MS/MS assay for quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: Application to the standardization of TCMs with endogenous toxicity. Chinese Medicine. 021 Jul 3;16(1):51. doi: 10.1186/s13020-021-00463-w. [4]Xiao Q, Ye T, Wang X, et al. A network pharmacology-based study on key pharmacological pathways and targets of Qi Fu Yin acting on Alzheimer's disease. Experimental Gerontology. 2021 Jul 1;149:111336. doi: 10.1016/j.exger.2021.111336. Epub 2021 Mar 27.

H2O:< 0.1 mg/mL (insoluble)
DMSO:31 mg/mL (66.45 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years