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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H26N4O3.ClH
Molecular Weight 502.993
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of STAUROSPORINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=LBAUWUDBVWHTSB-TTZYPCBDSA-N
InChI=1S/C28H26N4O3.ClH/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);1H/t17-,20-,26-,28+;/m1./s1

HIDE SMILES / InChI

Molecular Formula C28H26N4O3
Molecular Weight 466.5321
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
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
Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation.
2001 Apr
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
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
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
Regulation of phosphate uptake in primary cultured rabbit renal proximal tubule cells by glucocorticoids: evidence for nongenomic as well as genomic mechanisms.
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
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
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
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
Development of cyclin-dependent kinase modulators as novel therapeutic approaches for hematological malignancies.
2001 Jan
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
DNA-dependent protein kinase catalytic subunit is cleaved during UV-induced apoptosis.
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
Prostaglandin receptors and role of G protein-activated pathways on corpora lutea of pseudopregnant rabbit in vitro.
2001 Jan
Role of mitogen-activated protein kinases in activation of human neutrophils by antineutrophil cytoplasmic antibodies.
2001 Jan
Differential effects of bcl-2 on cell death triggered under ATP-depleting conditions.
2001 Jan 1
Differential p53-dependent mechanism of radiosensitization in vitro and in vivo by the protein kinase C-specific inhibitor PKC412.
2001 Jan 15
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
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
Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes.
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
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
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 Sat Jun 26 09:09:45 UTC 2021
Edited
by admin
on Sat Jun 26 09:09:45 UTC 2021
Record UNII
LB78KZ9G1K
Record Status Validated (UNII)
Record Version
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Name Type Language
STAUROSPORINE HYDROCHLORIDE
MI  
Common Name English
STAUROSPORINE HYDROCHLORIDE [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 HYDROCHLORIDE
Common Name English
STAUROSPORINE HCL
Common Name English
Code System Code Type Description
MERCK INDEX
M10198
Created by admin on Sat Jun 26 09:09:45 UTC 2021 , Edited by admin on Sat Jun 26 09:09:45 UTC 2021
PRIMARY Merck Index
FDA UNII
LB78KZ9G1K
Created by admin on Sat Jun 26 09:09:45 UTC 2021 , Edited by admin on Sat Jun 26 09:09:45 UTC 2021
PRIMARY
PUBCHEM
76962610
Created by admin on Sat Jun 26 09:09:45 UTC 2021 , Edited by admin on Sat Jun 26 09:09:45 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE