staurosporine   Click here for help

GtoPdb Ligand ID: 346

Synonyms: (+)-staurosporine | antibiotic 230 | antibiotic AM-2282
PDB Ligand
Compound class: Natural product
Comment: Staurosporine is a non-specific, ATP-competitive inhibitor of protein kinase C (PKC) isolated from a Streptomyces strain [10]. It inhibits all PKC enzyme isoforms [2,13], but has a more potent inhibitory effect on PKCs associated with the cell membrane compared to cytosolic PKCs.
Staurosporine analogues such as midostaurin and 7-hydroxystaurosporine are being investigated as therapeutics.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

staurosporine is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 2
Topological polar surface area 69.45
Molecular weight 466.2
XLogP 6.05
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES CNC1CC2OC(C1OC)(C)n1c3ccccc3c3c1c1n2c2ccccc2c1c1c3CNC1=O
Isomeric SMILES CN[C@@H]1C[C@H]2O[C@]([C@@H]1OC)(C)n1c3ccccc3c3c1c1n2c2ccccc2c1c1c3CNC1=O
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
InChI Key HKSZLNNOFSGOKW-FYTWVXJKSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
Staurosporine inhibits PKCs from the cell membrane fraction with an IC50 of 1.3nM [2]. The IC50 for cytosol derived PKC inhibition is 16.3nM in the same study.
Staurosporine has antifungal properties but does not demonstrate antibacterial activity [10].
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
M1 receptor Hs Allosteric modulator Positive 5.9 pKd - 8
⤷ pKd 5.9 [8]
M4 receptor Hs Allosteric modulator Neutral 5.3 pKd - 8
⤷ pKd 5.3 [8]
M2 receptor Hs Allosteric modulator Positive 5.1 pKd - 8
⤷ pKd 5.1 [8]
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
large tumor suppressor kinase 2 Hs Inhibitor Inhibition 7.8 pKd - 3
⤷ pKd 7.8 (Kd 1.7x10-8 M) [3]
large tumor suppressor kinase 1 Hs Inhibitor Inhibition 7.4 pKd - 3
⤷ pKd 7.4 (Kd 4.2x10-8 M) [3]
calcium/calmodulin-dependent protein kinase II beta subunit Hs Inhibitor Inhibition >10.0 pIC50 - 6
⤷ pIC50 >10.0 (IC50 <1x10-10 M) [6]
phosphorylase kinase catalytic subunit gamma 2 Hs Inhibitor Inhibition 10.0 pIC50 - 6
⤷ pIC50 10.0 (IC50 1x10-10 M) [6]
serine/threonine kinase 3 Hs Inhibitor Inhibition 9.4 pIC50 - 6
⤷ pIC50 9.4 (IC50 4.1x10-10 M) [6]
death associated protein kinase 1 Hs Inhibitor Inhibition 9.3 pIC50 - 6
⤷ pIC50 9.3 (IC50 5x10-10 M) [6]
protein kinase N1 Hs Inhibitor Inhibition 9.0 pIC50 - 6
⤷ pIC50 9.0 (IC50 1x10-9 M) [6]
mitogen-activated protein kinase kinase 4 Hs Inhibitor Inhibition >9.0 pIC50 - 11
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [11]
mitogen-activated protein kinase kinase 6 Hs Inhibitor Inhibition >9.0 pIC50 - 11
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [11]
p21 (RAC1) activated kinase 2 Hs Inhibitor Inhibition 9.0 pIC50 - 6
⤷ pIC50 9.0 (IC50 1x10-9 M) [6]
TRAF2 and NCK interacting kinase Hs Inhibitor Inhibition 8.9 pIC50 - 7
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [7]
large tumor suppressor kinase 2 Hs Inhibitor Inhibition 8.4 pIC50 - 9
⤷ pIC50 8.4 (IC50 3.76x10-9 M) [9]
large tumor suppressor kinase 1 Hs Inhibitor Inhibition 7.9 pIC50 - 9
⤷ pIC50 7.9 (IC50 1.28x10-8 M) [9]
protein kinase, cAMP-dependent, catalytic, beta subunit Hs Inhibitor Inhibition 7.5 pIC50 - 4
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [4]
protein kinase C iota Hs Inhibitor Inhibition 6.5 pIC50 - 12
⤷ pIC50 6.5 (IC50 3.46x10-7 M) [12]
homeodomain interacting protein kinase 1 Hs Inhibitor Inhibition 5.6 pIC50 - 6
⤷ pIC50 5.6 (IC50 2.639x10-6 M) [6]
Ligand mentioned in the following text fields
Acetylcholine receptors (muscarinic) comments