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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
Structure of STAUROSPORINE

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

HIDE SMILES / InChI

Molecular Formula C28H26N4O3
Molecular Weight 466.531
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Interferon-gamma, bacterial lipopolysaccharide, and tumor necrosis factor-alpha induce CD11a mRNA and protein via Na+/H+ exchange and protein kinase C-dependent mechanisms in tissue macrophages.
1999 Apr 13
Calcineurin-mediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: An apoptosis-independent model of dilated heart failure.
2000 Feb 18
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
Arsenite induces apoptosis of murine T lymphocytes through membrane raft-linked signaling for activation of c-Jun amino-terminal kinase.
2000 Oct 15
Up-regulation of Bcl-xL in response to subtoxic beta-amyloid: role in neuronal resistance against apoptotic and oxidative injury.
2001
Hemicholinium-3 mustard reveals two populations of cycling choline cotransporters in Limulus.
2001
High glucose stimulates Ca2+ uptake via cAMP and PLC/PKC pathways in primary cultured renal proximal tubule cells.
2001
Regulation of Bcl2 phosphorylation and potential significance for leukemic cell chemoresistance.
2001
Phosphorylation down-regulates the RNA binding function of the coat protein of potato virus A.
2001 Apr 27
An apoplastic Ca2+ sensor regulates internal Ca2+ release in aequorin-transformed tobacco cells.
2001 Apr 6
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
Effect of the overexpression of wild-type or mutant alpha-synuclein on cell susceptibility to insult.
2001 Feb
Interferon-gamma protects astrocytes from apoptosis and increases the formation of p21ras-GTP complex through ras oncogene family overexpression.
2001 Feb
Effect of serine protease inhibitors on posttraumatic brain injury and neuronal apoptosis.
2001 Feb
Prosaposin treatment induces PC12 entry in the S phase of the cell cycle and prevents apoptosis: activation of ERKs and sphingosine kinase.
2001 Feb
Key targets for the execution of radiation-induced tumor cell apoptosis: the role of p53 and caspases.
2001 Feb 1
Effects of staurosporine on exocytosis and endocytosis at frog motor nerve terminals.
2001 Feb 1
Pertussis toxin-sensitive G-protein and protein kinase C activity are involved in normal synapse elimination in the neonatal rat muscle.
2001 Feb 15
Natural protection from apoptosis by surfactant protein A in type II pneumocytes.
2001 Feb 15
Use of protein kinase C inhibitors results in rapid [Mg(2+)](i) mobilization in primary cultured rat aortic smooth muscle cells: are certain kinase C isoforms natural homeostatic regulators of cystolic free Mg(2+).
2001 Feb 16
Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties.
2001 Feb 16
Vascular endothelial growth factor KDR receptor signaling potentiates tumor necrosis factor-induced tissue factor expression in endothelial cells.
2001 Feb 16
Neuroprotective effects of NV-31, a bilobalide-derived compound: evidence for an antioxidative mechanism.
2001 Feb 2
Apoptosis-resistant mitochondria in T cells selected for resistance to Fas signaling.
2001 Feb 2
Phosphatidic acid and diacylglycerol directly activate NADPH oxidase by interacting with enzyme components.
2001 Feb 2
Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity.
2001 Feb 2
DNA-dependent protein kinase catalytic subunit is cleaved during UV-induced apoptosis.
2001 Jan
The role of Bax in glutamate-induced nerve cell death.
2001 Jan
Prostaglandin receptors and role of G protein-activated pathways on corpora lutea of pseudopregnant rabbit in vitro.
2001 Jan
Lysophosphatidylcholine induces apoptosis in AR42J cells.
2001 Jan
Differential regulation of microglial NO production by protein kinase C inhibitors.
2001 Jan
Differential p53-dependent mechanism of radiosensitization in vitro and in vivo by the protein kinase C-specific inhibitor PKC412.
2001 Jan 15
Inhibitory role of regucalcin in the regulation of Ca2+ dependent protein kinases activity in rat brain neurons.
2001 Jan 15
Caspase-3-mediated processing of poly(ADP-ribose) glycohydrolase during apoptosis.
2001 Jan 26
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
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
cAMP-independent phosphorylation activation of CFTR by G proteins in native human sweat duct.
2001 Mar
TGF-beta1 inhibits caspase-3 activation and neuronal apoptosis in rat hippocampal cultures.
2001 Mar
The "in vivo" and "ex vivo" roles of cylcooxygenase-2, nuclear factor-kappaB and protein kinases pathways in the up-regulation of B1 receptor-mediated contraction of the rabbit aorta.
2001 Mar 2
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.
Substance Class Chemical
Created
by admin
on Thu Jul 06 02:44:37 UTC 2023
Edited
by admin
on Thu Jul 06 02:44:37 UTC 2023
Record UNII
H88EPA0A3N
Record Status Validated (UNII)
Record Version
  • Download
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 Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
NCI_THESAURUS C221
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
Code System Code Type Description
FDA UNII
H88EPA0A3N
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
WIKIPEDIA
Staurosporine
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
DRUG BANK
DB02010
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
MESH
D019311
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
CAS
62996-74-1
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
CHEBI
57491
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
PUBCHEM
44259
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
EPA CompTox
DTXSID6041131
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
NCI_THESAURUS
C1237
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
CHEBI
15738
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY
MERCK INDEX
M10198
Created by admin on Thu Jul 06 02:44:37 UTC 2023 , Edited by admin on Thu Jul 06 02:44:37 UTC 2023
PRIMARY Merck Index
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