The specificities of protein kinase inhibitors: an update
Top Cited Papers
- 1 April 2003
- journal article
- research article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 371 (1) , 199-204
- https://doi.org/10.1042/bj20021535
Abstract
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; IC50 = 0.33μM) and p38-regulated/activated kinase (PRAK; IC50 = 1.0μM).Keywords
This publication has 37 references indexed in Scilit:
- p42/p44 MAPKs are intracellular targets of the CDK inhibitor purvalanolOncogene, 2002
- TAK1/JNK and p38 have opposite effects on rat hepatic stellate cellsHepatology, 2001
- Inhibition of UVB-Induced Oxidative Stress-Mediated Phosphorylation of Mitogen-Activated Protein Kinase Signaling Pathways in Cultured Human Epidermal Keratinocytes by Green Tea Polyphenol (−)-Epigallocatechin-3-gallateToxicology and Applied Pharmacology, 2001
- Specificity and mechanism of action of some commonly used protein kinase inhibitorsBiochemical Journal, 2000
- SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin‐1Published by Wiley ,2000
- Adenovirus-mediated Gene Transfer of cGMP-dependent Protein Kinase Increases the Sensitivity of Cultured Vascular Smooth Muscle Cells to the Antiproliferative and Pro-apoptotic Effects of Nitric Oxide/cGMPPublished by Elsevier ,1998
- Acquisition of Sensitivity of Stress-activated Protein Kinases to the p38 Inhibitor, SB 203580, by Alteration of One or More Amino Acids within the ATP Binding PocketPublished by Elsevier ,1998
- Lithium inhibits glycogen synthase kinase-3 activity and mimics Wingless signalling in intact cellsCurrent Biology, 1996
- Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase InhibitorJournal of Biological Chemistry, 1996
- PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in VivoJournal of Biological Chemistry, 1995