Staurosporine
Staurosporine (CAS 62996-74-1) is an alkaloid compound originally isolated from the bacterium Streptomyces staurospores and functions as a broad-spectrum inhibitor of serine/threonine protein kinases. It potently inhibits multiple kinases, including protein kinase C (PKC), protein kinase A (PKA), epidermal growth factor receptor kinase (EGF-R kinase), calmodulin-dependent protein kinase II (CaMKII), phosphorylase kinase, and ribosomal protein S6 kinase. Its activity against PKC exhibits an IC50 value of approximately 2.7 nM. In biomedical research, staurosporine is commonly employed to induce apoptosis in mammalian cancer cell lines and to investigate the roles and signaling pathways of protein kinases.
Reference
Takashi Toda, Mizuki Shimanuki, and Mitsuhiro Yanagida. Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases. Genes Dev. 1991 5: 60-73
Michelle M. Hill, Mirjana Andelkovic, Derek P. Brazil, Stefano Ferrari, Doriano Fabbro, and Brian A. Hemmings. Insulin-stimulated protein kinase B phosphorylation on Ser-473 is independent of its activity and occurs through a Staurosporine-insensitive kinase. J. Biol. Chem 2001, 276: 25643-25646.
Flavio Meggio, Arianna Donella Deana, Maria Ruzzene, Anna M. Brunati, Luca Cesaro, Barbara Guerra, Thomas Meyer, Helmut Mett, Doriano Fabbro, Pascal Furet, Grazyna Dobrowolska, and Lorenzo A. Pinna. Different susceptibility of protein kinases to staurosporine inhibition kinetic studies and molecular bases for the resistance of protein kinase CK2. Eur. J. Biochem. 234, 317-322 (1995)
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 466.53 |
| Cas No. | 62996-74-1 |
| Formula | C28H26N4O3 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥11.66 mg/mL in DMSO |
| Chemical Name | (5S,6R,7R,9R)-6-methoxy-5-methyl-7-(methylamino)-6,7,8,9,15,16-hexahydro-17-oxa-4b,9a,15-triaza-5,9-methanodibenzo[b,h]cyclonona[jkl]cyclopenta[e]-as-indacen-14(5H)-one |
| SDF | Download SDF |
| Canonical SMILES | O=C(NC1)C2=C1C3=C(C4=C2C5=C(C=CC=C5)N4[C@H]6C[C@@H](NC)[C@@H](OC)[C@]7(C)O6)N7C8=CC=CC=C83 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: | |
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Cell lines |
A31 cell lines, CHO-KDR cell lines, Mo-7e cell lines and A431 cell lines. |
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Preparation method |
The solubility of this compound in DMSO is |
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Reaction Conditions |
24 h; IC50=0.08 mM (A31 cell lines), IC50=0.30 mM (Mo-7e cell lines), IC50=1.0 mM (CHO-KDR cell lines). |
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Applications |
Staurosporine inhibited the ligand-induced autophosphorylation of the receptors for platelet-derived growth factor (PDGF) (IC50=0.08 mM) in A31 cell lines, stem cell factor (c-Kit, IC50=0.30 mM) in Mo-7e cell lines, and for VEGF (KDR, IC50=1.0 mM) in CHO-KDR cell lines, but did not affect the ligand-induced autophosphorylation of the receptors for insulin, IGF-I, or epidermal growth factor (EGF) in A431 cell lines. |
| Animal experiment: | |
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Animal models |
Athymic nude mice |
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Dosage form |
75 mg/kg/day; oral taken. |
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Applications |
The treatment with Staurosporine (75 mg/kg/day p.o.) completely inhibits the angiogenic response to VEGF, but not to bFGF. Thus, Staurosporine may suppress tumor growth by inhibiting tumor angiogenesis (via its effects on the VEGF-R 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 Staurosporine, as well as the synergy with cytotoxic agents. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Andrejauskas-Buchdunger E, Regenass U. Differential inhibition of the epidermal growth factor-, platelet-derived growth factor-, and protein kinase C-mediated signal transduction pathways by the staurosporine derivative CGP 41251[J]. Cancer research, 1992, 52(19): 5353-5358. [2] Fabbro D, Buchdunger E, Wood J, et al. Inhibitors of protein kinases: CGP 41251, a protein kinase inhibitor with potential as an anticancer agent[J]. Pharmacology & therapeutics, 1999, 82(2): 293-301. |
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| Description | Staurosporine is a potent inhibitor of PKC for PKCα, PKCγ and PKCη with IC50 values of 2 nM, 5 nM and 4 nM, respectively. | |||||
| Targets | PKCα | PKCγ | PKCη | PKCδ | PKCε | PKCζ |
| IC50 | 2 nM | 5 nM | 4 nM | 20 nM | 73 nM | 1086 nM |
Quality Control & MSDS
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