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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
Protein phosphatase-protein kinase interplay modulates alpha 1b-adrenoceptor phosphorylation: effects of okadaic acid.
2000 Feb
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
High glucose stimulates Ca2+ uptake via cAMP and PLC/PKC pathways in primary cultured renal proximal tubule cells.
2001
Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine.
2001 Feb
Signal transduction pathways through TRK-A and TRK-B receptors in human neuroblastoma cells.
2001 Feb
Effect of serine protease inhibitors on posttraumatic brain injury and neuronal apoptosis.
2001 Feb
Neuroprotective effects of NV-31, a bilobalide-derived compound: evidence for an antioxidative mechanism.
2001 Feb 2
Expression of macrophage asialoglycoprotein-binding protein is induced through MAPK classical pathway.
2001 Feb 9
Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis.
2001 Jan
Differential p53-dependent mechanism of radiosensitization in vitro and in vivo by the protein kinase C-specific inhibitor PKC412.
2001 Jan 15
Caspase-3-mediated processing of poly(ADP-ribose) glycohydrolase during apoptosis.
2001 Jan 26
Electrical activity regulates AChR gene expression via JNK, PKCzeta and Sp1 in skeletal chick muscle.
2001 Jan 5
Cell autonomous apoptosis defects in acid sphingomyelinase knockout fibroblasts.
2001 Jan 5
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
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 Fri Dec 15 19:41:46 GMT 2023
Edited
by admin
on Fri Dec 15 19:41:46 GMT 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 Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
NCI_THESAURUS C221
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
Code System Code Type Description
FDA UNII
H88EPA0A3N
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
WIKIPEDIA
Staurosporine
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
DRUG BANK
DB02010
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
MESH
D019311
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
CAS
62996-74-1
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
CHEBI
57491
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
PUBCHEM
44259
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
EPA CompTox
DTXSID6041131
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
NCI_THESAURUS
C1237
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
CHEBI
15738
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY
MERCK INDEX
m10198
Created by admin on Fri Dec 15 19:41:47 GMT 2023 , Edited by admin on Fri Dec 15 19:41:47 GMT 2023
PRIMARY Merck Index
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