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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H26N4O3
Molecular Weight 466.5321
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of STAUROSPORINE

SMILES

C[C@]12[C@@]([H])([C@@]([H])(C[C@]([H])(n3c4ccccc4c5c6c(CN=C6O)c7c8ccccc8n1c7c53)O2)NC)OC

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

HIDE SMILES / InChI

Description
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

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

Curator's Comment:: Staurosporine was discovered at the Kitasato Institute in 1977 while screening for microbial alkaloids using chemical detection methods.

Approval Year

TargetsConditions
PubMed

PubMed

TitleDatePubMed
Modulation of tau phosphorylation within its microtubule-binding domain by cellular thiols.
1999 Nov
Actinomycin D and staurosporine, potent apoptosis inducers in vitro, are potentially effective chemotherapeutic agents against glioblastoma multiforme.
2000
Microtubule/MAP-affinity regulating kinase (MARK) is activated by phenylarsine oxide in situ and phosphorylates tau within its microtubule-binding domain.
2000 Apr
Protein phosphatase-protein kinase interplay modulates alpha 1b-adrenoceptor phosphorylation: effects of okadaic acid.
2000 Feb
Calcineurin-mediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: An apoptosis-independent model of dilated heart failure.
2000 Feb 18
Mechanism of doxorubicin-induced inhibition of sarcoplasmic reticulum Ca(2+)-ATPase gene transcription.
2000 Jan 7-21
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
Caspase-mediated proteolytic activation of calcineurin in thapsigargin-mediated apoptosis in SH-SY5Y neuroblastoma cells.
2000 Jul 15
Induction and regulation of xenobiotic-metabolizing cytochrome P450s in the human A549 lung adenocarcinoma cell line.
2000 Mar
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
Arsenite induces apoptosis of murine T lymphocytes through membrane raft-linked signaling for activation of c-Jun amino-terminal kinase.
2000 Oct 15
Adenosine triphosphate activates mitogen-activated protein kinase in human granulosa-luteal cells.
2001 Apr
Expression of myogenic constrictor tone in the aorta of hypertensive rats.
2001 Apr
Regulation of SERCA Ca2+ pump expression by cytoplasmic Ca2+ in vascular smooth muscle cells.
2001 Apr
Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation.
2001 Apr
Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells.
2001 Apr 13
An apoplastic Ca2+ sensor regulates internal Ca2+ release in aequorin-transformed tobacco cells.
2001 Apr 6
Inhibition of K+ currents by homocysteine in rat ventricular myocytes.
2001 Feb
Characterization of adenylyl cyclases in cultured human granulosa cells.
2001 Feb
Ischemia-induced ventricular fibrillation in isolated perfused rat heart: role of alpha1A-adrenoceptor mediated activation of protein kinase C.
2001 Feb
Involvement of erythropoietin-induced cytosolic free calcium mobilization in activation of mitogen-activated protein kinase and DNA synthesis in vascular smooth muscle cells.
2001 Feb
Enzyme-linked immunosorbent assay for the determination of p21-activated kinase activity.
2001 Feb
Effect of serine protease inhibitors on posttraumatic brain injury and neuronal apoptosis.
2001 Feb
Regulation of phosphate uptake in primary cultured rabbit renal proximal tubule cells by glucocorticoids: evidence for nongenomic as well as genomic mechanisms.
2001 Feb
Regulation of PDGFR-alpha in rat pulmonary myofibroblasts by staurosporine.
2001 Feb
Key targets for the execution of radiation-induced tumor cell apoptosis: the role of p53 and caspases.
2001 Feb 1
Overexpression of BCL-X(L) underlies the molecular basis for resistance to staurosporine-induced apoptosis in PC-3 cells.
2001 Feb 15
DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells.
2001 Feb 15
Truncated trkB.T1 is dominant negative inhibitor of trkB.TK+-mediated cell survival.
2001 Feb 9
Expression of macrophage asialoglycoprotein-binding protein is induced through MAPK classical pathway.
2001 Feb 9
Effects of Mannheimia haemolytica leukotoxin on apoptosis and oncosis of bovine neutrophils.
2001 Jan
The role of Bax in glutamate-induced nerve cell death.
2001 Jan
Neurotrophin-3 mediates the autocrine survival of the catecholaminergic CAD CNS neuronal cell line.
2001 Jan
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
Lysophosphatidylcholine induces apoptosis in AR42J cells.
2001 Jan
Role of mitogen-activated protein kinases in activation of human neutrophils by antineutrophil cytoplasmic antibodies.
2001 Jan
Pyrrolo-1,5-benzoxazepines induce apoptosis in chronic myelogenous leukemia (CML) cells by bypassing the apoptotic suppressor bcr-abl.
2001 Jan
Effects of extracellular calcium and potassium on the sodium pump of rat adrenal glomerulosa cells.
2001 Jan
Apoptosis enhancement by the HIV-1 Nef protein.
2001 Jan 1
Differential effects of bcl-2 on cell death triggered under ATP-depleting conditions.
2001 Jan 1
Inhibitory role of regucalcin in the regulation of Ca2+ dependent protein kinases activity in rat brain neurons.
2001 Jan 15
Activation of dopamine D(1)-like receptor causes phosphorylation of alpha(1)-subunit of Na(+),K(+)-ATPase in rat renal proximal tubules.
2001 Jan 5
Cell autonomous apoptosis defects in acid sphingomyelinase knockout fibroblasts.
2001 Jan 5
Effects of short- and long-term exposure to c-AMP and c-GMP on the noradrenaline transporter.
2001 Mar
Venom from the platypus, Ornithorhynchus anatinus, induces a calcium-dependent current in cultured dorsal root ganglion cells.
2001 Mar
Protein phosphatase inhibitors facilitate DHPG-induced LTD in the CA1 region of the hippocampus.
2001 Mar
TGF-beta1 inhibits caspase-3 activation and neuronal apoptosis in rat hippocampal cultures.
2001 Mar
TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis.
2001 Mar 16
IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein.
2001 Mar 23
Calcium/calmodulin-dependent protein kinase inhibition potentiates thapsigargin-mediated cell death in SH-SY5Y human neuroblastoma cells.
2001 Mar 30
Patents

Sample Use Guides

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
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.
Name Type Language
STAUROSPORINE
MI  
Common Name English
CGP-39360
Code English
STAUROSPORIN
Common Name English
STAUROSPORINE [MI]
Common Name English
(9S,10R,11R,13R)- 2,3,10,11,12,13-HEXAHYDRO-10-METHOXY-9-METHYL-11-(METHYLAMINO)-9,13-EPOXY-1H,9H-DIINDOLO(1,2,3-GH:3',2',1'-LM)PYRROLO(3,4-J)(1,7)BENZODIAZONIN-1-ONE
Common Name English
(+)-STAUROSPORINE
Common Name English
AM-2282
Code English
Classification Tree Code System Code
NCI_THESAURUS C1404
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
NCI_THESAURUS C221
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
Code System Code Type Description
FDA UNII
H88EPA0A3N
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY
WIKIPEDIA
Staurosporine
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY
DRUG BANK
DB02010
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY
MESH
D019311
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY
CAS
62996-74-1
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY
PUBCHEM
44259
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY
EPA CompTox
62996-74-1
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY
NCI_THESAURUS
C1237
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY
MERCK INDEX
M10198
Created by admin on Sat Jun 26 11:53:18 UTC 2021 , Edited by admin on Sat Jun 26 11:53:18 UTC 2021
PRIMARY Merck Index