Identification

Name
Staurosporine
Accession Number
DB02010  (EXPT02970, EXPT02972)
Type
Small Molecule
Groups
Experimental
Description

An indolocarbazole that is a potent protein kinase C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)

Structure
Thumb
Synonyms
Not Available
External IDs
AM-2282 / CGP-39360
Categories
UNII
H88EPA0A3N
CAS number
62996-74-1
Weight
Average: 466.531
Monoisotopic: 466.200490718
Chemical Formula
C28H26N4O3
InChI Key
HKSZLNNOFSGOKW-FYTWVXJKSA-N
InChI
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
IUPAC Name
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.1²,⁶.0⁷,²⁸.0⁸,¹³.0¹⁵,¹⁹.0²⁰,²⁷.0²¹,²⁶]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one
SMILES
[H][[email protected]]1(C[[email protected]@]2([H])O[[email protected]](C)(N3C4=CC=CC=C4C4=C5CNC(=O)C5=C5C6=CC=CC=C6N2C5=C34)[[email protected]]1([H])OC)NC

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UTyrosine-protein kinase LckNot AvailableHuman
USerine/threonine-protein kinase pim-1Not AvailableHuman
UTyrosine-protein kinase ITK/TSKNot AvailableHuman
UTyrosine-protein kinase SYKNot AvailableHuman
UMAP kinase-activated protein kinase 2Not AvailableHuman
UGlycogen synthase kinase-3 betaNot AvailableHuman
UTyrosine-protein kinase CSKNot AvailableHuman
UCyclin-dependent kinase 2Not AvailableHuman
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformNot AvailableHuman
U3-phosphoinositide-dependent protein kinase 1Not AvailableHuman
UProtein kinase C theta typeNot AvailableHuman
UTyrosine-protein kinase ZAP-70Not AvailableHuman
UMuscarinic acetylcholine receptor M1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Staurosporine.Approved
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Staurosporine.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Staurosporine.Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Staurosporine.Approved
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Staurosporine.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Staurosporine.Approved, Investigational
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Staurosporine.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Staurosporine.Approved
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Staurosporine.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Staurosporine.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Staurosporine.Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Staurosporine.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Staurosporine.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Staurosporine.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Staurosporine.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Staurosporine.Approved, Investigational
VincristineThe serum concentration of Vincristine can be increased when it is combined with Staurosporine.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference

Chikara Murakata, Toshimitsu Takiguchi, Shigeo Katsumata, Akira Mihara, Keiichi Takahashi, Hiromitsu Saito, Shiro Akinaga, Masami Okabe, Yutaka Saito, "Process for producing staurosporine derivatives." U.S. Patent US5344926, issued December, 1990.

US5344926
General References
Not Available
External Links
KEGG Compound
C02079
PubChem Compound
44259
PubChem Substance
46504923
ChemSpider
40272
BindingDB
2579
ChEBI
15738
ChEMBL
CHEMBL388978
Therapeutic Targets Database
DNC001380
PharmGKB
PA165109623
HET
STU
Wikipedia
Staurosporine
PDB Entries
1aq1 / 1byg / 1e8z / 1nvr / 1nxk / 1oky / 1q3d / 1qpd / 1qpj / 1sm2
show 64 more

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0439 mg/mLALOGPS
logP3.14ALOGPS
logP3.97ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)14.14ChemAxon
pKa (Strongest Basic)9.55ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area69.45 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity132.37 m3·mol-1ChemAxon
Polarizability50.47 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9737
Blood Brain Barrier-0.5243
Caco-2 permeable-0.5213
P-glycoprotein substrateSubstrate0.7192
P-glycoprotein inhibitor IInhibitor0.6683
P-glycoprotein inhibitor IINon-inhibitor0.6315
Renal organic cation transporterNon-inhibitor0.7748
CYP450 2C9 substrateNon-substrate0.7682
CYP450 2D6 substrateNon-substrate0.7667
CYP450 3A4 substrateSubstrate0.7987
CYP450 1A2 substrateNon-inhibitor0.563
CYP450 2C9 inhibitorNon-inhibitor0.6732
CYP450 2D6 inhibitorNon-inhibitor0.8232
CYP450 2C19 inhibitorNon-inhibitor0.6896
CYP450 3A4 inhibitorNon-inhibitor0.5634
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5897
Ames testNon AMES toxic0.6318
CarcinogenicityNon-carcinogens0.8573
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6695 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9986
hERG inhibition (predictor II)Inhibitor0.5198
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolocarbazoles. These are polycyclic aromatic compounds containing an indole fused to a carbazole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Carbazoles
Direct Parent
Indolocarbazoles
Alternative Parents
Pyrrolo[2,3-a]carbazoles / Pyrroloindoles / Isoindolones / Indoles / Benzenoids / Oxanes / Pyrroles / Heteroaromatic compounds / Amino acids and derivatives / Secondary carboxylic acid amides
show 8 more
Substituents
Indolocarbazole / Pyrrolo[2,3-a]carbazole / Pyrroloindole / Isoindolone / Indole / Isoindoline / Isoindole or derivatives / Benzenoid / Oxane / Heteroaromatic compound
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organic heterooctacyclic compound, indolocarbazole alkaloid (CHEBI:15738)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-ce...
Gene Name
LCK
Uniprot ID
P06239
Uniprot Name
Tyrosine-protein kinase Lck
Molecular Weight
58000.15 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcription factor binding
Specific Function
Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity throug...
Gene Name
PIM1
Uniprot ID
P11309
Uniprot Name
Serine/threonine-protein kinase pim-1
Molecular Weight
45411.905 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Non-membrane spanning protein tyrosine kinase activity
Specific Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-c...
Gene Name
ITK
Uniprot ID
Q08881
Uniprot Name
Tyrosine-protein kinase ITK/TSK
Molecular Weight
71830.405 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates seve...
Gene Name
SYK
Uniprot ID
P43405
Uniprot Name
Tyrosine-protein kinase SYK
Molecular Weight
72065.76 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Signal transducer activity
Specific Function
Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA dam...
Gene Name
MAPKAPK2
Uniprot ID
P49137
Uniprot Name
MAP kinase-activated protein kinase 2
Molecular Weight
45567.415 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by pho...
Gene Name
GSK3B
Uniprot ID
P49841
Uniprot Name
Glycogen synthase kinase-3 beta
Molecular Weight
46743.865 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C...
Gene Name
CSK
Uniprot ID
P41240
Uniprot Name
Tyrosine-protein kinase CSK
Molecular Weight
50703.975 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Details
8. Cyclin-dependent kinase 2
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Metal ion binding
Specific Function
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, N...
Gene Name
CDK2
Uniprot ID
P24941
Uniprot Name
Cyclin-dependent kinase 2
Molecular Weight
33929.215 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recr...
Gene Name
PIK3CG
Uniprot ID
P48736
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Molecular Weight
126452.625 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB...
Gene Name
PDPK1
Uniprot ID
O15530
Uniprot Name
3-phosphoinositide-dependent protein kinase 1
Molecular Weight
63151.305 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin-protein transferase activity
Specific Function
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells act...
Gene Name
PRKCQ
Uniprot ID
Q04759
Uniprot Name
Protein kinase C theta type
Molecular Weight
81864.145 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor binding
Specific Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development....
Gene Name
ZAP70
Uniprot ID
P43403
Uniprot Name
Tyrosine-protein kinase ZAP-70
Molecular Weight
69871.63 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Lazareno S, Popham A, Birdsall NJ: Allosteric interactions of staurosporine and other indolocarbazoles with N-[methyl-(3)H]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site. Mol Pharmacol. 2000 Jul;58(1):194-207. [PubMed:10860942]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Budworth J, Davies R, Malkhandi J, Gant TW, Ferry DR, Gescher A: Comparison of staurosporine and four analogues: their effects on growth, rhodamine 123 retention and binding to P-glycoprotein in multidrug-resistant MCF-7/Adr cells. Br J Cancer. 1996 May;73(9):1063-8. [PubMed:8624264]

Drug created on June 13, 2005 07:24 / Updated on November 09, 2017 03:08