U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
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
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
Phosphorylation down-regulates the RNA binding function of the coat protein of potato virus A.
2001 Apr 27
Interactions between 2-fluoroadenine 9-beta-D-arabinofuranoside and the kinase inhibitor UCN-01 in human leukemia and lymphoma cells.
2001 Feb
Inhibition of K+ currents by homocysteine in rat ventricular myocytes.
2001 Feb
Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine.
2001 Feb
Characterization of adenylyl cyclases in cultured human granulosa cells.
2001 Feb
Signal transduction pathways through TRK-A and TRK-B receptors in human neuroblastoma 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
Na+/K+ATPase activity inhibition and isoform-specific translocation of protein kinase C following angiotensin II administration in isolated eel enterocytes.
2001 Feb
Effect of the overexpression of wild-type or mutant alpha-synuclein on cell susceptibility to insult.
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
Prosaposin treatment induces PC12 entry in the S phase of the cell cycle and prevents apoptosis: activation of ERKs and sphingosine kinase.
2001 Feb
S-Phase arrest by nucleoside analogues and abrogation of survival without cell cycle progression by 7-hydroxystaurosporine.
2001 Feb 1
Key targets for the execution of radiation-induced tumor cell apoptosis: the role of p53 and caspases.
2001 Feb 1
Protein kinase C signaling controls skeletal muscle fiber types.
2001 Feb 1
Effects of staurosporine on exocytosis and endocytosis at frog motor nerve terminals.
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
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
Neuroprotective effects of NV-31, a bilobalide-derived compound: evidence for an antioxidative mechanism.
2001 Feb 2
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
Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis.
2001 Jan
Effects of Mannheimia haemolytica leukotoxin on apoptosis and oncosis of bovine neutrophils.
2001 Jan
Calcitonin potentiates oxygen-glucose deprivation-induced neuronal death.
2001 Jan
DNA-dependent protein kinase catalytic subunit is cleaved during UV-induced apoptosis.
2001 Jan
Modulatory effect of protein kinase C activator on contractility of rat vas deferens.
2001 Jan
Inhibitory role of regucalcin in the regulation of Ca2+ dependent protein kinases activity in rat brain neurons.
2001 Jan 15
Aspirin promotes TFF2 gene activation in human gastric cancer cell lines.
2001 Jan 19
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
Electrical activity regulates AChR gene expression via JNK, PKCzeta and Sp1 in skeletal chick muscle.
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
Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes.
2001 Mar
Resistance to induced apoptosis in the human neuroblastoma cell line SK-N-SH in relation to neuronal differentiation. Role of Bcl-2 protein family.
2001 Mar
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
Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C.
2001 Mar 1
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
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