Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C28H26N4O3 |
Molecular Weight | 466.531 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]12C[C@@H](NC)[C@@H](OC)[C@](C)(O1)N3C4=C(C=CC=C4)C5=C3C6=C(C7=CC=CC=C7N26)C8=C5CNC8=O
InChI
InChIKey=HKSZLNNOFSGOKW-FYTWVXJKSA-N
InChI=1S/C28H26N4O3/c1-28-26(34-3)17(29-2)12-20(35-28)31-18-10-6-4-8-14(18)22-23-16(13-30-27(23)33)21-15-9-5-7-11-19(15)32(28)25(21)24(22)31/h4-11,17,20,26,29H,12-13H2,1-3H3,(H,30,33)/t17-,20-,26-,28+/m1/s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/7649849 | https://www.ncbi.nlm.nih.gov/pubmed/11313863Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8194597
https://www.ncbi.nlm.nih.gov/pubmed/22888461
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7649849 | https://www.ncbi.nlm.nih.gov/pubmed/11313863
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8194597
https://www.ncbi.nlm.nih.gov/pubmed/22888461
Staurosporine is an alkaloid isolated from the culture broth of Streptomyces staurosporesa. It exerts antimicrobial, hypotensive, and cytotoxic activity. The main biological activity of staurosporine is the inhibition of protein kinases through the prevention of ATP binding to the kinase. This is achieved through the stronger affinity of staurosporine to the ATP-binding site on the kinase. Staurosporine is a prototypical ATP-competitive kinase inhibitor in that it binds to many kinases with high affinity, though with little selectivity. It is a potent, cell permeable protein kinase C inhibitor with an IC50 of 0.7 nM. At higher concentration (1-20 nM), staurosporine also inhibits other kinases such as PKA, PKG, CAMKII and Myosin light chain kinase (MLCK). At 50-100 nM, it is a functional neurotrophin agonist, promoting neurite outgrowth in neuroblastoma, pheochromocytoma and brain primary neuronal cultures. At 0.2- 1 uM, staurosporine induces cell apoptosis. Staurosporine is also a potent GSK-3β inhibitor with a reported IC50 value of 15 nM. In research, staurosporine is used to induce apoptosis. It has been found that one way in which staurosporine induces apoptosis is by activating caspase-3. Staurosporine was discovered to have biological activities ranging from anti-fungal to anti-hypertensive. The interest in these activities resulted in a large investigative effort in chemistry and biology and the discovery of the potential for anti-cancer treatment. Staurosporine induces apoptosis by multiple pathways and that the inhibition of more than one kinase is responsible for its potent activity. Because the mechanism of action of staurosporine is distinct from traditional anticancer drugs, this may warrant further preclinical evaluations of the antitumor potential of new staurosporine derivatives either alone or in combination with death ligands or conventional chemotherapeutic drugs.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22888461 | https://www.ncbi.nlm.nih.gov/pubmed/8726076
Curator's Comment: Staurosporine might be considered as a prototype neurotropic drug in view of its ability to induce neurite outgrowth and to increase tau protein levels. Because it mimics some of the neuroprotective effects of NGF and might blocks certain signals required to enhance cellular levels and/or beta amyloid processing, staurosporine might play a beneficial role in the treatment of Alzheimer's disease.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19132059
Curator's Comment: Staurosporine was discovered at the Kitasato Institute in 1977 while screening for microbial alkaloids using chemical detection methods.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL262 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22888461 |
15.0 nM [IC50] | ||
Target ID: CHEMBL3231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26318056 |
19.0 nM [IC50] | ||
Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26318056 |
24.0 nM [IC50] | ||
Target ID: CHEMBL267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26318056 |
9.7 nM [IC50] | ||
Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26318056 |
4.3 nM [IC50] | ||
Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26318056 |
11.0 nM [IC50] | ||
Target ID: CHEMBL308 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26318056 |
4.9 nM [IC50] | ||
Target ID: CHEMBL2996 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25190070 |
64.0 nM [IC50] | ||
Target ID: CHEMBL2093867 Sources: https://media.cellsignal.com/pdf/9953.pdf |
0.7 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Actinomycin D and staurosporine, potent apoptosis inducers in vitro, are potentially effective chemotherapeutic agents against glioblastoma multiforme. | 2000 |
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Calcineurin-mediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: An apoptosis-independent model of dilated heart failure. | 2000 Feb 18 |
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Mechanism of doxorubicin-induced inhibition of sarcoplasmic reticulum Ca(2+)-ATPase gene transcription. | 2000 Jan 7-21 |
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Allosteric interactions of staurosporine and other indolocarbazoles with N-[methyl-(3)H]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site. | 2000 Jul |
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Caspase-mediated proteolytic activation of calcineurin in thapsigargin-mediated apoptosis in SH-SY5Y neuroblastoma cells. | 2000 Jul 15 |
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Deficiency of the stress kinase p38alpha results in embryonic lethality: characterization of the kinase dependence of stress responses of enzyme-deficient embryonic stem cells. | 2000 Mar 6 |
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The super anti-apoptotic factor Bcl-xFNK constructed by disturbing intramolecular polar interactions in rat Bcl-xL. | 2000 Nov 24 |
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Up-regulation of Bcl-xL in response to subtoxic beta-amyloid: role in neuronal resistance against apoptotic and oxidative injury. | 2001 |
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Expression of myogenic constrictor tone in the aorta of hypertensive rats. | 2001 Apr |
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Regulation of SERCA Ca2+ pump expression by cytoplasmic Ca2+ in vascular smooth muscle cells. | 2001 Apr |
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Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation. | 2001 Apr |
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Characterization of adenylyl cyclases in cultured human granulosa cells. | 2001 Feb |
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Enzyme-linked immunosorbent assay for the determination of p21-activated kinase activity. | 2001 Feb |
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Key targets for the execution of radiation-induced tumor cell apoptosis: the role of p53 and caspases. | 2001 Feb 1 |
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Overexpression of BCL-X(L) underlies the molecular basis for resistance to staurosporine-induced apoptosis in PC-3 cells. | 2001 Feb 15 |
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Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. | 2001 Feb 16 |
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Vascular endothelial growth factor KDR receptor signaling potentiates tumor necrosis factor-induced tissue factor expression in endothelial cells. | 2001 Feb 16 |
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Apoptosis-resistant mitochondria in T cells selected for resistance to Fas signaling. | 2001 Feb 2 |
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Phosphatidic acid and diacylglycerol directly activate NADPH oxidase by interacting with enzyme components. | 2001 Feb 2 |
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Truncated trkB.T1 is dominant negative inhibitor of trkB.TK+-mediated cell survival. | 2001 Feb 9 |
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Modulatory effect of protein kinase C activator on contractility of rat vas deferens. | 2001 Jan |
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The role of Bax in glutamate-induced nerve cell death. | 2001 Jan |
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Neurotrophin-3 mediates the autocrine survival of the catecholaminergic CAD CNS neuronal cell line. | 2001 Jan |
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Cellular distribution of constitutively active mutant parathyroid hormone (PTH)/PTH-related protein receptors and regulation of cyclic adenosine 3',5'-monophosphate signaling by beta-arrestin2. | 2001 Jan |
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Growth hormone- and prolactin-induced proliferation of insulinoma cells, INS-1, depends on activation of STAT5 (signal transducer and activator of transcription 5). | 2001 Jan |
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Activation of human neutrophils by technical toxaphene. | 2001 Jan |
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Prostaglandin receptors and role of G protein-activated pathways on corpora lutea of pseudopregnant rabbit in vitro. | 2001 Jan |
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Lysophosphatidylcholine induces apoptosis in AR42J cells. | 2001 Jan |
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Pyrrolo-1,5-benzoxazepines induce apoptosis in chronic myelogenous leukemia (CML) cells by bypassing the apoptotic suppressor bcr-abl. | 2001 Jan |
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Differential regulation of microglial NO production by protein kinase C inhibitors. | 2001 Jan |
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Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. | 2001 Jan 12 |
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Inhibitory role of regucalcin in the regulation of Ca2+ dependent protein kinases activity in rat brain neurons. | 2001 Jan 15 |
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Caspase-3-mediated processing of poly(ADP-ribose) glycohydrolase during apoptosis. | 2001 Jan 26 |
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Electrical activity regulates AChR gene expression via JNK, PKCzeta and Sp1 in skeletal chick muscle. | 2001 Jan 5 |
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Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes. | 2001 Mar |
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G-protein-coupled receptor kinase 3- and protein kinase C-mediated desensitization of the PACAP receptor type 1 in human Y-79 retinoblastoma cells. | 2001 Mar |
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TGF-beta1 inhibits caspase-3 activation and neuronal apoptosis in rat hippocampal cultures. | 2001 Mar |
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TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis. | 2001 Mar 16 |
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Natural ceramide reverses Fas resistance of acid sphingomyelinase(-/-) hepatocytes. | 2001 Mar 16 |
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Calcium/calmodulin-dependent protein kinase inhibition potentiates thapsigargin-mediated cell death in SH-SY5Y human neuroblastoma cells. | 2001 Mar 30 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24174874
Mice: A low intravenous dose (0.8 mg/kg) inhibited U87 tumors in a murine flank model.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24479128
Curator's Comment: At 0.2-1 uM, staurosporine induces cell apoptosis https://media.cellsignal.com/pdf/9953.pdf
PC3 cells exposed to 2 uM staurosporine were 32% ± 10% apoptotic under normoxic conditions but only 1.5% ± 12% apoptotic under hypoxic conditions.
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NCI_THESAURUS |
C1404
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NCI_THESAURUS |
C221
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H88EPA0A3N
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Staurosporine
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DB02010
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D019311
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62996-74-1
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57491
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44259
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DTXSID6041131
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C1237
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15738
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m10198
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PRIMARY | Merck Index |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)