The specificities of protein kinase inhibitors: an update.
We have previously examined the specificities of 28 commercially available compounds, reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases [Davies, Reddy, Caivano and Cohen (2000) Biochem. J. 351, 95-105]. In the present study, we have extended this analysis to a further 14 compounds. Of these, indirubin-3'-monoxime, SP 600125, KT 5823 and ML-9 were found to inhibit a number of protein kinases and conclusions drawn from their use in cell-based assays are likely to be erroneous. Kenpaullone, Alsterpaullone, Purvalanol, Roscovitine, pyrazolopyrimidine 1 (PP1), PP2 and ML-7 were more specific, but still inhibited two or more protein kinases with similar potency. Our results suggest that the combined use of Roscovitine and Kenpaullone may be useful for identifying substrates and physiological roles of cyclin-dependent protein kinases, whereas the combined use of Kenpaullone and LiCl may be useful for identifying substrates and physiological roles of glycogen synthase kinase 3. The combined use of SU 6656 and either PP1 or PP2 may be useful for identifying substrates of Src family members. Epigallocatechin 3-gallate, one of the main polyphenolic constituents of tea, inhibited two of the 28 protein kinases in the panel, dual-specificity, tyrosine-phosphorylated and regulated kinase 1A (DYRK1A; IC(50)=0.33 microM) and p38-regulated/activated kinase (PRAK; IC(50)=1.0 microM).
Bain
Jenny
J
Division of Signal Transduction Therapy, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK.
McLauchlan
Hilary
H
Elliott
Matthew
M
Cohen
Philip
P
D000470:Alkaloids / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002227:Carbazoles; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D007211:Indoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D007701:Kinetin; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011687:Purines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; C412373:AG 1879; D000470:Alkaloids; D000873:Anthracenes; D001381:Azepines; D001552:Benzazepines; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D009281:Naphthalenes; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; C120793:alsterpaullone; C474021:indirubin-3'-monoxime; C119620:kenpaullone; C056218:ML 9; C070571:ML 7; C073601:KT 5823; C432165:pyrazolanthrone; C090046:olomoucine; D002392:Catechin; C045651:epigallocatechin gallate; D019061:src-Family Kinases; D018844:Cyclin-Dependent Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D007701:Kinetin