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

Large-scale screening data

DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 3,13

Key to terms and symbols Click column headers to sort
Target Name in screen Sp. Type Action Value Parameter
STE20 like kinase SLK Hs Inhibitor Inhibition 10.6 pKd
serine/threonine kinase 10 LOK Hs Inhibitor Inhibition 10.4 pKd
calcium/calmodulin dependent protein kinase kinase 1 CAMKK1 Hs Inhibitor Inhibition 10.4 pKd
NUAK family, SNF1-like kinase, 2 SNARK Hs Inhibitor Inhibition 10.1 pKd
phosphorylase kinase catalytic subunit gamma 2 PHKG2 Hs Inhibitor Inhibition 9.9 pKd
calcium/calmodulin-dependent protein kinase II alpha subunit CAMK2A Hs Inhibitor Inhibition 9.8 pKd
calcium/calmodulin dependent protein kinase kinase 2 CAMKK2 Hs Inhibitor Inhibition 9.8 pKd
serine/threonine kinase 3 MST2 Hs Inhibitor Inhibition 9.7 pKd
serine/threonine kinase 4 MST1 Hs Inhibitor Inhibition 9.7 pKd
fms related receptor tyrosine kinase 3 FLT3(R834Q) Hs Inhibitor Inhibition 9.7 pKd
Displaying the top 10 targets  View all targets in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 1,5

Key to terms and symbols Click column headers to sort
Target Name in screen Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
protein kinase C gamma PKCγ/PKCg Hs Inhibitor Inhibition -3.2 1.5 1.0
calcium/calmodulin dependent protein kinase kinase 1 nd/CAMKK1 Hs Inhibitor Inhibition -3.1
ribosomal protein S6 kinase A3 Rsk2/RSK2 Hs Inhibitor Inhibition -1.3 0.0 0.0
TANK binding kinase 1 TBK1/TBK1 Hs Inhibitor Inhibition -0.5 1.5 0.5
serine/threonine kinase 4 MST1/MST1(STK4) Hs Inhibitor Inhibition -0.2 -0.5 1.0
microtubule affinity regulating kinase 2 PAR-1Bα/MARK2(PAR-1Ba) Hs Inhibitor Inhibition 0.0 -1.0 0.0
microtubule affinity regulating kinase 4 nd/MARK4 Hs Inhibitor Inhibition 0.0
salt inducible kinase 2 nd/SIK2 Hs Inhibitor Inhibition 0.1
ribosomal protein S6 kinase B1 p70S6K/p70S6K(RPS6KB1) Hs Inhibitor Inhibition 0.1 1.5 3.0
protein kinase N1 nd/PKN1(PRK1) Hs Inhibitor Inhibition 0.1
Displaying the top 10 targets  View all targets in screen »