staurosporine   

GtoPdb Ligand ID: 346

Synonyms: (+)-staurosporine | antibiotic 230 | antibiotic AM-2282
Comment: Staurosporine is a non-specific, ATP-competitive inhibitor of protein kinase C (PKC) isolated from a Streptomyces strain [9]. It inhibits all PKC enzyme isoforms [2,12], 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.
2D Structure
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Physico-chemical Properties
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
SMILES / InChI / InChIKey
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
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.
Selectivity at GPCRs
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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
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
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 - 10
pIC50 >9.0 (IC50 <1x10-9 M) [10]
mitogen-activated protein kinase kinase 6 Hs Inhibitor Inhibition >9.0 pIC50 - 10
pIC50 >9.0 (IC50 <1x10-9 M) [10]
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]
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 - 11
pIC50 6.5 (IC50 3.46x10-7 M) [11]
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