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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:: 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

Targets

Targets

Primary TargetPharmacologyConditionPotency
15 nM [IC50]
19 nM [IC50]
24 nM [IC50]
9.69999999999999929 nM [IC50]
4.29999999999999982 nM [IC50]
11 nM [IC50]
4.90000000000000036 nM [IC50]
64 nM [IC50]
0.699999999999999956 nM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
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
The super anti-apoptotic factor Bcl-xFNK constructed by disturbing intramolecular polar interactions in rat Bcl-xL.
2000 Nov 24
Expression of myogenic constrictor tone in the aorta of hypertensive rats.
2001 Apr
Interactions between 2-fluoroadenine 9-beta-D-arabinofuranoside and the kinase inhibitor UCN-01 in human leukemia and lymphoma cells.
2001 Feb
Ischemia-induced ventricular fibrillation in isolated perfused rat heart: role of alpha1A-adrenoceptor mediated activation of protein kinase C.
2001 Feb
Effect of the overexpression of wild-type or mutant alpha-synuclein on cell susceptibility to insult.
2001 Feb
Key targets for the execution of radiation-induced tumor cell apoptosis: the role of p53 and caspases.
2001 Feb 1
Natural protection from apoptosis by surfactant protein A in type II pneumocytes.
2001 Feb 15
Vascular endothelial growth factor KDR receptor signaling potentiates tumor necrosis factor-induced tissue factor expression in endothelial cells.
2001 Feb 16
Apoptosis-resistant mitochondria in T cells selected for resistance to Fas signaling.
2001 Feb 2
DNA-dependent protein kinase catalytic subunit is cleaved during UV-induced apoptosis.
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
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
Differential regulation of microglial NO production by protein kinase C inhibitors.
2001 Jan
Characterization of a rice (Oryza sativa L.) Bowman-Birk proteinase inhibitor: tightly light regulated induction in response to cut, jasmonic acid, ethylene and protein phosphatase 2A inhibitors.
2001 Jan 24
Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors?
2001 Jan 5
Venom from the platypus, Ornithorhynchus anatinus, induces a calcium-dependent current in cultured dorsal root ganglion cells.
2001 Mar
Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C.
2001 Mar 1
TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis.
2001 Mar 16
Natural ceramide reverses Fas resistance of acid sphingomyelinase(-/-) hepatocytes.
2001 Mar 16
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