The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.
The specificities of protein kinase inhibitors: an update
Open accessAbstract
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).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The latest result demonstrates that the JNK specificity of SP600125 is not so excellent and this compound inhibits some protein kinases with similar or greater potency than JNK (Bain et al , 2003).”
From Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125 (2004) · cites this paper as Bain et al , 2003
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Meijer, L., Nelson, D. J., Riazanski, V., Gabdoulkhakova, A. G., Héry-Arnaud, G., Berre, R. L., Loaëc, N., Oumata, N., Galons, H., Nowak, E., et al. (2016) · Journal of Innate Immunity · doi:10.1159/000444256 · Cited by 5,008
Specificity and mechanism of action of some commonly used protein kinase inhibitors
DAVIES, S. P., Reddy, H., Caivano, M., & Cohen, P. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510095 · Cited by 4,366
Self-citationAlessi, D. R., Cuenda, A., Cohen, P., Dudley, D. T., & Saltiel, A. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27489 · Cited by 3,374
Self-citationIdentification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase
Favata, M. F., Horiuchi, K. Y., Manos, E. J., Daulerio, A. J., Stradley, D. A., Feeser, W. S., Dyk, D. E. V., Pitts, W. J., Earl, R. A., Hobbs, F. W., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18623 · Cited by 3,016
A synthetic inhibitor of the mitogen-activated protein kinase cascade.
Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J., & Saltiel, A. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.7686 · Cited by 2,679
SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251194298 · Cited by 2,558
A molecular mechanism for the effect of lithium on development.
Klein, P. S., & Melton, D. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8455 · Cited by 2,334
Protein kinases — the major drug targets of the twenty-first century?
Cohen, P. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd773 · Cited by 2,232
Self-citationCuenda, A., Rouse, J., Doza, Y. N., Meier, R., Cohen, P., Gallagher, T. F., Young, P. R., & Lee, J. C. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00357-f · Cited by 2,086
Self-citationDiscovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase Inhibitor
Hanke, J. H., Gardner, J. P., Dow, R. L., Changelian, P. S., Brissette, W. H., Weringer, E. J., Pollok, B. A., & Connelly, P. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.695 · Cited by 1,939
Flagged first, then by citations
1 of the 42 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
Roberts, P. J., & Der, C. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210422 · Cited by 2,788
“…and CI-1040/PD184352) or p38 (SB203580 and SB 202190) (Davies et al., 2000), the preclinical observations made with the SP600125 JNK inhibitor are likely to be less informative regarding the biological roles of JNK, owing to the considerable off-target activity of this compound (Bain et al., 2003).”
BackgroundThe selectivity of protein kinase inhibitors: a further update
Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I. V., Arthur, J. S. C., Alessi, D. R., & Cohen, P. (2007) · Biochemical Journal · doi:10.1042/bj20070797 · Cited by 2,522
“The substrates used for other protein kinases were described previously[1, 2 ].”
BackgroundMethodInfluentialSelf-citationComprehensive analysis of kinase inhibitor selectivity
Davis, M. I., Hunt, J. P., Herrgard, S., Ciceri, P., Wodicka, L. M., Pallares, G., Hocker, M., Treiber, D. K., & Zarrinkar, P. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1990 · Cited by 2,409
A quantitative analysis of kinase inhibitor selectivity
Karaman, M. W., Herrgard, S., Treiber, D. K., Gallant, P., Atteridge, C. E., Campbell, B. T., Chan, K. W., Ciceri, P., Davis, M. I., Edeen, P. T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1358 · Cited by 2,466
“dtd" [ ]> A first step toward understanding how kinase inhibitor selectivity affects biological activity is to identify and quantify potential off-target kinase interaction”
BackgroundA small molecule–kinase interaction map for clinical kinase inhibitors
Fabian, M. A., Biggs, W., Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M. B., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1068 · Cited by 1,923
“Compounds must be tested experimentally against many kinases to assess molecular specificity and to identify off-target interaction”
BackgroundHawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.009 · Cited by 1,589
Self-citationMammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update
Kyriakis, J. M., & Avruch, J. (2012) · Physiological Reviews · doi:10.1152/physrev.00028.2011 · Cited by 1,529
“Both of these compounds have been used extensively to identify pathways in which the ERKs play a dominant role (8, 9, 54).”
BackgroundMAPK cascade signalling and synaptic plasticity
Thomas, G. M., & Huganir, R. L. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1346 · Cited by 1,454
Physiology of cell volume regulation in vertebrates
Hoffmann, E. K., Lambert, I. H., & Pedersen, S. F. (2009) · Physiological Reviews · doi:10.1152/physrev.00037.2007 · Cited by 1,441
Fry, D. W., Harvey, P. J., Keller, P. R., Elliott, W. L., Meade, M., Trachet, E., Albassam, M., Zheng, X., Leopold, W. R., Pryer, N. K., et al. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.1427.3.11 · Cited by 1,236
GSK-3α regulates production of Alzheimer's disease amyloid-β peptides
Phiel, C. J., Wilson, C., Lee, V. M. ‐., & Klein, P. S. (2003) · Nature · doi:10.1038/nature01640 · Cited by 1,211
“To test the hypothesis that lithium reduces Aβ production through inhibition of GSK-3, we treated CHO-APP 695 cells with the structurally unrelated GSK-3 inhibitor kenpaullon”
MethodComprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity
Anastassiadis, T., Deacon, S. W., Devarajan, K., Ma, H., & Peterson, J. R. (2011) · Nature Biotechnology · doi:10.1038/nbt.2017 · Cited by 919
Banaszynski, L. A., Chen, L.-C., Maynard-Smith, L. A., Ooi, A. G. L., & Wandless, T. J. (2006) · Cell · doi:10.1016/j.cell.2006.07.025 · Cited by 902
“However, the question of specificity remains of the utmost importance; in many cases, proteomic analysis reveals that a small-molecule regulator of protein function targets at least one, if not many, off-target proteins (Davies et al., 2000; Bain et al., 2003; Godl et al., 2003).”
GSK-3-Selective Inhibitors Derived from Tyrian Purple Indirubins
Meijer, L., Skaltsounis, A., Magiatis, P., Polychronopoulos, P., Knockaert, M., Leost, M., Ryan, X. P., Vonica, A., Brivanlou, A. H., Dajani, R., et al. (2003) · Chemistry & Biology · doi:10.1016/j.chembiol.2003.11.010 · Cited by 814
GSK3 inhibitors: development and therapeutic potential
Cohen, P., & Goedert, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1415 · Cited by 801
“By contrast, lithium ions do not inhibit CDKs, but instead inhibit a few protein kinases distinct from those affected by the GSK3 inhibitors mentioned abov”
BackgroundSelf-citationRedox regulation of FoxO transcription factors
Klotz, L.-O., Sánchez-Ramos, C., Prieto-Arroyo, I., Urbánek, P., Steinbrenner, H., & Monsalve, M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.06.019 · Cited by 747
“DYRK-1a is a Pro-directed kinase [96,97] that phosphorylates Ser329 in FoxO1a, which appears to slightly support nuclear exclusion and to moderately affect FoxO activity [98].”
BackgroundSystematic Discovery of In Vivo Phosphorylation Networks
Linding, R., Jensen, L. J., Ostheimer, G. J., van Vugt, M. A. T. M., Jørgensen, C., Miron, I. M., Diella, F., Colwill, K., Taylor, L., Elder, K., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.052 · Cited by 739
“…there is an ever-widening gap in our understanding of in vivo phosphorylation networks, which is difficult to close in a systematic way by current experimental methods, despite advances in high-throughput in vitro assays (Ptacek et al., 2005) and selective kinase inhibitors (Bain et al., 2003).”
BackgroundEngelman, J. A., Zejnullahu, K., Gale, C.-M., Lifshits, E., Gonzales, A. J., Shimamura, T., Zhao, F., Vincent, P. W., Naumov, G. N., Bradner, J. E., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1885 · Cited by 730
Rose, B. A., Force, T. L., & Wang, Y. (2010) · Physiological Reviews · doi:10.1152/physrev.00054.2009 · Cited by 730
“This is not a new concept, since for years the Cohen laboratory has performed detailed studies exposing the nonselectivity of reportedly selective inhibitors (20, 21, 92).”
BackgroundCell Biology of Tight Junction Barrier Regulation and Mucosal DiseasePreprint
Buckley, A., & Turner, J. R. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a029314 · Cited by 724
“However, studies of MLCK were hampered by the lack of specific inhibitors, knockdown/knockout cell lines, and knockout mice, which resulted in the necessary reliance on nonspecific agents such as ML-7 (Bain et al. 2003).”
BackgroundLTP Inhibits LTD in the Hippocampus via Regulation of GSK3β
Peineau, S., Taghibiglou, C., Bradley, C. A., Wong, T. P., Liu, L., Lu, J., Lo, E., Wu, D., Saule, E., Bouschet, T., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.029 · Cited by 709
“2G and H), a concentration 40 times the IC 50 for inhibition of CDK2 (Bain et al., 2003).”
Features of Selective Kinase Inhibitors
Knight, Z. A., & Shokat, K. M. (2005) · Chemistry & Biology · doi:10.1016/j.chembiol.2005.04.011 · Cited by 674
“Two valuable studies have profiled many of the most commonly used kinase inhibitors against 28 protein kinases in this way [62, 63].”
BackgroundProtein Kinase G from Pathogenic Mycobacteria Promotes Survival Within Macrophages
Walburger, A., Koul, A., Ferrari, G., Nguyen, L., Prescianotto-Baschong, C., Huygen, K., Klebl, B., Thompson, C., Bacher, G., & Pieters, J. (2004) · Science · doi:10.1126/science.1099384 · Cited by 595
Pharmacological inhibitors of glycogen synthase kinase 3
Meijer, L., Flajolet, M., & Greengard, P. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.07.006 · Cited by 586
“However, because many GSK-3 inhibitors also affect CDKs (Table 1) [33], control experiments should be carried out using CDK inhibitors that do not target GSK-3 (such as roscovitine and purvalanol)[ 29 ].Insomecircumstances,CDK5‐GSK-3 dual specificity could be an advantage, as illustrated later.”
BackgroundInfluentialChi, H., Barry, S. P., Flach, R. J. R., Wu, J. J., Jones, E. A., Bennett, A. M., & Flavell, R. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510965103 · Cited by 568
Self-renewal of teratocarcinoma and embryonic stem cells
Chambers, I., & Smith, A. G. (2004) · Oncogene · doi:10.1038/sj.onc.1207930 · Cited by 535
Targeting dual-specificity phosphatases: Manipulating MAP kinase signalling and immune responses
Jeffrey, K. L., Camps, M., Rommel, C., & Mackay, C. R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2289 · Cited by 533
“Nevertheless there are shortcomings to this approach, mainly because of a lack of specificity that is due to the conservation of the ATP-binding pockets among the many kinase”
BackgroundLiao, J.-L. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm0608107 · Cited by 512
Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6
Toogood, P. L., Harvey, P. J., Repine, J. T., Sheehan, D. J., VanderWel, S. N., Zhou, H., Keller, P. R., McNamara, D. J., Sherry, D., Zhu, T., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm049354h · Cited by 513
Cellular signalling of the receptor for advanced glycation end products (RAGE)
Xie, J., Méndez, J. D., Méndez-Valenzuela, V., & Aguilar-Hernández, M. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.06.013 · Cited by 525
Targeting JNK for therapeutic benefit: from junk to gold?
Manning, A. M., & Davis, R. J. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1132 · Cited by 585
“Recently, SP-600125 was tested under different conditions against a broader range of kinases, in which it inhibited several other kinases with a similar or greater potency than the JNK”
BackgroundC-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity
Gunawan, B. K., Liu, Z., Han, D., Hanawa, N., Gaarde, W. A., & Kaplowitz, N. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.03.045 · Cited by 471
Doble, B. W., Patel, S., Wood, G. A., Kockeritz, L. K., & Woodgett, J. R. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.04.001 · Cited by 458
“Moreover, GSK-3 inhibitors are prone to non-specific “off-target” effects that become more pronounced as the working concentration of inhibitor increases (Bain et al., 2003).”
BackgroundLeon, R. M., García, A. G., & Marco, J. L. (2011) · Medicinal Research Reviews · doi:10.1002/med.20248 · Cited by 447
“Frequently considered as highly selective for CDKs, roscovitine has been shown to interact with several other kinases (DYRK1A, CK1, pyridoxal kinase).(319) Purines are a large family of biologically active molecules, constituting a scaffold of a wide variety of promising drugs, including kinase inhibitors as 2,6,9-tri…”
BackgroundClayburgh, D. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24970 · Cited by 419
“Thus, PIK overcomes the problems of nonspecificity that have plagued studies using ML-7 and ML-9 (69).”
Backgroundc-Jun N-terminal Kinase (JNK) Signaling as a Therapeutic Target for Alzheimer’s Disease
Yarza, R., Vela, S., Solas, M., & Ramírez, M. J. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00321 · Cited by 428
“However, it is to note that SP600125 has shown a limited specificity toward JNK, as also inhibits not only MKK4 and MKK7, but also other protein kinases unrelated to JNK, such as SGK, p70 ribosomal protein S6 kinase (S6K1), AMPK, CDK2, CK1d, and DYRK1A (Bain et al., 2003).”
BackgroundSu, L., Nalle, S. C., Shen, L., Turner, E. S., Singh, G., Breskin, L. A., Khramtsova, E. A., Khramtsova, G. F., Tsai, P., Fu, Y., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.04.011 · Cited by 393
New approaches to molecular cancer therapeutics
Collins, I., & Workman, P. (2006) · Nature Chemical Biology · doi:10.1038/nchembio840 · Cited by 394
“Nevertheless, in vitro selectivity profiling using panels of isolated kinase”
BackgroundPuttini, M., Coluccia, A. M. L., Boschelli, F., Cleris, L., Marchesi, E., Donella‐Deana, A., Ahmed, S., Redaelli, S., Piazza, R., Magistroni, V., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1199 · Cited by 382
“Procedures for purification and assay of 30 of the 52kinases have been described (31, 32 ). Kinase assays were done using ATP concentrations close to the Km value for each kinase.”
MethodMechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure
Fernández-Sánchez, M. E., Barbier, S., Whitehead, J., Béalle, G., Michel, A., Latorre-Ossa, H., Rey, C., Fouassier, L., Clapéron, A., Brullé, L., et al. (2015) · Nature · doi:10.1038/nature14329 · Cited by 371
Regulation of JNK and p38 MAPK in the immune system: Signal integration, propagation and termination
Huang, G., Shi, L. Z., & Chi, H. (2009) · Cytokine · doi:10.1016/j.cyto.2009.08.002 · Cited by 383
“However, for mechanistic studies, pharmacological inhibitors are well known to cause non-specific or non-physiological effects [16,17].”
BackgroundCytoskeletal Regulation of Epithelial Barrier Function During Inflammation
Ivanov, A. I., Parkos, C. A., & Nusrat, A. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.100168 · Cited by 366
“While inhibiting MLCK, these ATP-competitive agents also inactivate other kinases.(101) ML-9, for example, has been shown to inhibit ROCK-II activity more potently than MLCK.”
BackgroundInfluentialA systematic interaction map of validated kinase inhibitors with Ser/Thr kinases
Fedorov, O., Marsden, B. D., Pogačić, V., Rellos, P., Müller, S., Bullock, A. N., Schwaller, J., Sundström, M., & Knapp, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708800104 · Cited by 362
L1000CDS2: LINCS L1000 characteristic direction signatures search engine
Duan, Q., Reid, S. P., Clark, N. R., Wang, Z., Fernandez, N., Rouillard, A. D., Readhead, B., Tritsch, S. R., Hodos, R. A., Hafner, M. A., et al. (2016) · npj Systems Biology and Applications · doi:10.1038/npjsba.2016.15 · Cited by 367
Roscovitine Targets, Protein Kinases and Pyridoxal Kinase
Bach, S., Knockaert, M., Reinhardt, J., Lozach, O., Schmitt, S., Baratte, B., Koken, M. H. M., Coburn, S. P., Tang, L., Jiang, T., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500806200 · Cited by 357
GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS
Eldar-Finkelman, H., & Martı́nez, A. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00032 · Cited by 362
“Systemic analysis that profiled protein kinase inhibitors also confirmed the high selectivity of CHIRs toward GSK-3 (Bain et al., 2003, 2007).”
Harley, M. E., Allan, L. A., Sanderson, H. S., & Clarke, P. R. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.112 · Cited by 360
“SP600125 also partially inhibited phosphorylation at these sites; this reagent inhibits JNK, but also other kinases, including CDKs (Bain et al, 2003).”
BackgroundCell Apoptosis: Requirement of H2AX in DNA Ladder Formation, but Not for the Activation of Caspase-3
Lu, C., Zhu, F., Cho, Y., Tang, F., Zykova, T. A., Ma, W., Bode, A. M., & Dong, Z. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.023 · Cited by 363
“Some reports (Bain et al., 2003; Davies et al., 2000) indicated that SP600125 is a non-specific inhibitor in vitro and affects other kinases such as p70 S6K.”
BackgroundChoi, K., Jung, M. G., Lee, Y., Yoon, J. C., Kwon, S. H., Kang, H., Kim, M., Cha, J., Kim, Y. J., Jun, W. J., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2442 · Cited by 354
JNK signalling in cancer: in need of new, smarter therapeutic targets
Bubici, C., & Papa, S. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12432 · Cited by 355
“MAPKs are activated via a BJP British Journal ofPharmacology DOI:10.1111/bph.12432 www.brjpharmacol.org 24 British Journal of Pharmacology (2014) 171 24–37 © 2013 The British Pharmacological Society kinase signalling cascade in which a MAP3K activates a MAP2K, that in turn activates a MAPK.”
BackgroundInfluentialMurray, J. T., CAMPBELL, D. G., Morrice, N. A., Auld, G. C., Shpiro, N., Márquez, R., Peggie, M. W., Bain, J., Bloomberg, G. B., Grahammer, F., et al. (2004) · Biochemical Journal · doi:10.1042/bj20041057 · Cited by 340
Self-citationde Vries, E., Tscherne, D. M., Wienholts, M. J., Jiménez, V. C., Scholte, F. E. M., García‐Sastre, A., Rottier, P. J. M., & de Haan, C. A. M. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1001329 · Cited by 339
“MLCK inhibitors ML-7 and ML-9 have been reported to be highly specific for their target kinase [30].”
Nuclear and cytosolic JNK signalling in neurons
Coffey, E. T. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3729 · Cited by 351
An efficient proteomics method to identify the cellular targets of protein kinase inhibitors
Godl, K., Wissing, J. B., Kurtenbach, A., Habenberger, P., Blencke, S., Gutbrod, H., Salassidis, K., Stein-Gerlach, M., Missio, A., Cotten, M. L., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2535024100 · Cited by 337
Strategies to overcome resistance to targeted protein kinase inhibitors
Daub, H., Specht, K., & Ullrich, A. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1579 · Cited by 337
“This can be done in high throughput by screening large collections of recombinant kinases against drug candidates in paralle”
BackgroundThe purines: Potent and versatile small molecule inhibitors and modulators of key biological targets
Legraverend, M., & Grierson, D. S. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2005.12.060 · Cited by 332
The Nrf2–Keap1 defence pathway: Role in protection against drug-induced toxicity
Copple, I. M., Goldring, C. E., Kitteringham, N. R., & Park, B. K. (2007) · Toxicology · doi:10.1016/j.tox.2007.10.029 · Cited by 336
Cole, A. R., Frame, S., & Cohen, P. (2004) · Biochemical Journal · doi:10.1042/bj20031259 · Cited by 324
Self-citationActivation-Loop Autophosphorylation Is Mediated by a Novel Transitional Intermediate Form of DYRKs
Lochhead, P. A., Sibbet, G. J., MORRICE, N. A., & Cleghon, V. (2005) · Cell · doi:10.1016/j.cell.2005.03.034 · Cited by 330
Mitogen-Activated Protein Kinases and Their Role in Radiation Response
Munshi, A., & Ramesh, R. (2013) · Genes & Cancer · doi:10.1177/1947601913485414 · Cited by 327
“Preclinical observations made with a JNK inhibitor (SP600125) are likely to be less informative regarding the biological roles of JNK due to the considerable off-target activity of this compound.(42) One JNK inhibitor, CC-401, is however in phase II evaluations in acute myelogenous leukemia and has also been considere…”
BackgroundMyosin light chain kinase: pulling the strings of epithelial tight junction function
Cunningham, K. E., & Turner, J. R. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06526.x · Cited by 345
The Many Faces of H89: A Review
Lochner, A., & Moolman, J. A. (2006) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2006.00261.x · Cited by 317
Multiple Wnts are involved in Hydra organizer formation and regeneration
Lengfeld, T., Watanabe, H., Simakov, O., Lindgens, D., Gee, L., Law, L. Y., Schmidt, H. A., Özbek, S., Bode, H. R., & Holstein, T. W. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.02.004 · Cited by 300
“(ii) Treatment with alsterpaullone, a specific inhibitor of GSK-3β (Leost et al., 2000; Bain et al., 2003), results in the body column, acquiring organizer characteristics as measured by transplantation experiments (Broun et al.”
BackgroundHui, L., Zatloukal, K., Scheuch, H., Stępniak-Konieczna, E., & Wagner, E. F. (2008) · Journal of Clinical Investigation · doi:10.1172/jci37156 · Cited by 313
BIRB796 Inhibits All p38 MAPK Isoforms in Vitro and in Vivo
Kuma, Y., Sabio, G., Bain, J., Shpiro, N., Márquez, R., & Cuenda, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414221200 · Cited by 307
Self-citationMechanisms of drug inhibition of signalling molecules
Sebolt, J. S., & English, J. M. (2006) · Nature · doi:10.1038/nature04874 · Cited by 309
“This novel binding mode seemed to confer desirable properties, such as enhanced selectivity relative to ATP-mimetic inhibitor”
BackgroundProbing the Probes: Fitness Factors For Small Molecule Tools
Workman, P., & Collins, I. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.05.013 · Cited by 304
Podolin, P. L., Callahan, J. F., Bolognese, B. J., Li, Y. H., Carlson, K., Davis, T. G., Mellor, G. W., Evans, C., & Roshak, A. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.074484 · Cited by 297
Identifying off-target effects and hidden phenotypes of drugs in human cells
MacDonald, M. L., Lamerdin, J. E., Owens, S., Keon, B. H., Bilter, G. K., Shang, Z., Huang, Z., Yu, H. W., Dias, J., Minami, T., et al. (2006) · Nature Chemical Biology · doi:10.1038/nchembio790 · Cited by 294
de la Torre, R., Sola, S. D., Pons‐Espinal, M., Duchon, A., de Lagrán, M. M., Farré, M., Fitó, M., Benejam, B., Langohr, K., Rodríguez, J. C., et al. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300325 · Cited by 297
“EGCG is a potent and selective inhibitor of DYRK1A activity [22].”
Backgroundde la Torre, R., de Sola, S., Hernández, G., Farré, M., Pujol, J., Rodríguez, J. C., Espadaler, J. M., Langohr, K., Cuenca‐Royo, A., Príncipe, A., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30034-5 · Cited by 291
Formation of the head organizer in hydra involves the canonical Wnt pathway.
Broun, M., Gee, L., Reinhardt, B., & Bode, H. R. (2005) · Development · doi:10.1242/dev.01848 · Cited by 287
“, 2000) but has no effect on GSK-3β (Bain et al., 2003).”
BackgroundMethodThe role of DYRK1A in neurodegenerative diseases
Węgiel, J., Gong, C., & Hwang, Y. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07955.x · Cited by 307
Regulation of smooth muscle calcium sensitivity: KCl as a calcium-sensitizing stimulus
Ratz, P. H., Berg, K. M., Urban, N. H., & Miner, A. S. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00529.2004 · Cited by 287
“Y-27632 inhibits the tonic phase much more than the early phase of a KCl-induced contraction in rabbit femoral and renal arteries (202) and rat caudal artery (121), whereas 30 M ML-9, a MLC kinase and ROK inhibitor (15, 200), attenuates both early and tonic force (121).”
BackgroundRewired ERK-JNK Signaling Pathways in Melanoma
Lopez‐Bergami, P., Huang, C. C., Goydos, J. S., Yip, D., Bar‐Eli, M., Herlyn, M., Smalley, K. S. M., Mahale, A. M., Eroshkin, A. M., Aaronson, S. A., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.03.009 · Cited by 285
“, 2000), it has been suggested that a structurally unrelated GSK3 inhibitor such as Kenpaullone should be used in combination with LiCl to confirm a GSK3 involvement (Bain et al., 2003).”
BackgroundThe JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer
Hammouda, M., Ford, A. E., Liu, Y., & Zhang, J. Y. (2020) · Cells · doi:10.3390/cells9040857 · Cited by 296
Hirota, T., Lewis, W. G., Liu, A. C., Lee, J. W., Schultz, P. G., & Kay, S. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811410106 · Cited by 285
“In contrast, roscovitine, that inhibits CDK but not GSK-3 (27), caused a long period phenotype (Table 1).”
BackgroundInfluentialHarmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation
Göckler, N., Jofré, G., Papadopoulos, C., Soppa, U., Tejedor, F., & Becker, W. (2009) · The FEBS Journal · doi:10.1111/j.1742-4658.2009.07346.x · Cited by 266
A reinvestigation of the multisite phosphorylation of the transcription factor c‐Jun
Morton, S., Davis, R. J., McLaren, A., & Cohen, P. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg388 · Cited by 281
Self-citationDevelopment of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A
Ogawa, Y., Nonaka, Y., Goto, T., Ohnishi, E., Hiramatsu, T., Kii, I., Yoshida, M., Ikura, T., Onogi, H., Shibuyà, H., et al. (2010) · Nature Communications · doi:10.1038/ncomms1090 · Cited by 276
“Other commonly used Dyrk1A inhibitors include roscovitine , purvalanol A and epigallocatechin gallate ( EGCG”
A review of connectivity map and computational approaches in pharmacogenomics
Musa, A., Ghoraie, L. S., Zhang, S., Galzko, G., Yli-Harja, O. P., Dehmer, M., Haibe‐Kains, B., & Emmert‐Streib, F. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbw112 · Cited by 275
“A GSK3B/ CDK2 inhibitor has shown a dose-dependent efficacy in inhibiting Ebola infection in vitro without causing cellular toxicity in human cell lines [67].”
BackgroundStructural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
Heo, Y., Kim, S., Seo, C. I., Kim, Y. K., Sung, B., Lee, H. S., Lee, J. I., Park, S., Kim, J. H., Hwang, K. Y., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600212 · Cited by 275
“The latest result demonstrates that the JNK specificity of SP600125 is not so excellent and this compound inhibits some protein kinases with similar or greater potency than JNK ( Bain et al, 2003 ).”
BackgroundResultInfluentialOverexpression of Dyrk1A contributes to neurofibrillary degeneration in down syndrome
Liu, F., Liang, Z., Wegiel, J., Hwang, Y., Iqbal, K., Grundke‐Iqbal, I., Ramakrishna, N., & Gong, C. (2008) · The FASEB Journal · doi:10.1096/fj.07-104539 · Cited by 272
“To verify the specificity of the assay, we added 10 M epigallocatechin-3-gallate (EGCG), a selective Dyrk1A inhibitor (22) into the assay mixture and found that EGCG inhibited 80% of the kinase activity in the brain extracts (Fig.”
MethodRybel, B. D., Audenaert, D., Vert, G., Rozhon, W., Mayerhofer, J., Peelman, F., Coutuer, S., Denayer, T., Jansen, L., Nguyen, L., et al. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.04.008 · Cited by 273
“basic protein (MBP), AURORA1 with histone H3, and of the human kinases as described previously (Bain et al., 2003; Demidov et al., 2005; Kiegerl et al., 2000).”
BackgroundA novel CDK5‐dependent pathway for regulating GSK3 activity and kinesin‐driven motility in neurons
Morfini, G. A., Szebenyi, G., Brown, H. J., Pant, H. C., Pigino, G. F., DeBoer, S. R., Beffert, U., & Brady, S. T. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600237 · Cited by 268
“In adipocytes or epithelial cells, GSK3 may be constitutively active (Ali et al, 2001), but increased GSK3 activity in neurons leads to neurite retraction (Munoz-Montano et al, 1999), apoptosis (Lucas et al, 2001), increased embryonic lethality (Hoeflich et al, 2000) and behavioral abnormalities…”
BackgroundDrugging the PI3 Kinome: From Chemical Tools to Drugs in the Clinic
Workman, P., Clarke, P., Raynaud, F., & van Montfort, R. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4355 · Cited by 287
“In a recent update (16) of the earlier compendium (14, 15)”
Ito, G., Okai, T., Fujino, G., Takeda, K., Ichijo, H., Katada, T., & Iwatsubo, T. (2007) · Biochemistry · doi:10.1021/bi061960m · Cited by 263
Contri, A., Brunati, A. M., Trentin, L., Cabrelle, A., Miorin, M., Cesaro, L., Pinna, L. A., Zambello, R., Semenzato, G., & Donella‐Deana, A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22094 · Cited by 260
“Accordingly, the combined use of these two inhibitors has been suggested for identifying the specific physiological roles of Src kinases (21).”
Gunn, W., Conley, A., Deininger, L., Olson, S. D., Prockop, D. J., & Gregory, C. A. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0220 · Cited by 260
Skov, S., Pedersen, M. T., Andresen, L. O., Straten, P. T., Woetmann, A., & Ødum, N. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0599 · Cited by 260
“By screening inhibitors of stress-related enzymes, we found that LiCl and kenpaullone, two structurally different inhibitors of GSK-3 kinase activity ( 38 ), potently inhibited FR901228-induced MICA/B expression in a concentration-dependent manner (Fig. 3A).”
BackgroundFransvea, E., Angelotti, U. F., Antonaci, S., & Giannelli, G. (2008) · Hepatology · doi:10.1002/hep.22201 · Cited by 254
Assay of protein kinases using radiolabeled ATP: a protocol
Hastie, C. J., McLauchlan, H., & Cohen, P. (2006) · Nature Protocols · doi:10.1038/nprot.2006.149 · Cited by 253
“In these assays, the reactions are done at room temperature and the [γ- 32 P]ATP is usually replaced by [γ- 33 P]ATP, as the latter isotope is a weaker β-emitter and thus has much less stringent requirements for shieldin”
BackgroundSelf-citationThe Jak/STAT pathway is involved in synaptic plasticity
Nicolas, C. S., Peineau, S., Amici, M., Csaba, Z., Fafouri, A., Javalet, C., Collett, V. J., Hildebrandt, L., Seaton, G., Choi, S.-L., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.024 · Cited by 246
Rena, G., Bain, J., Elliott, M., & Cohen, P. (2004) · EMBO Reports · doi:10.1038/sj.embor.7400048 · Cited by 250
“A similar value was obtained with the standard synthetic peptide substrate for CK1 (Bain et al, 2003).”
MethodSelf-citationStructurally Sophisticated Octahedral Metal Complexes as Highly Selective Protein Kinase Inhibitors
Feng, L., Geisselbrecht, Y., Blanck, S., Wilbuer, A., Atilla‐Gokcumen, G. E., Filippakopoulos, P., Kräling, K., Çelik, M. A., Harms, K., Maksimoska, J., et al. (2011) · Journal of the American Chemical Society · doi:10.1021/ja1112996 · Cited by 244
Preconditioning Doses of NMDA Promote Neuroprotection by Enhancing Neuronal Excitability
Soriano, F. X., Papadia, S., Hofmann, F., Hardingham, N. R., Bading, H., & Hardingham, G. E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0455-06.2006 · Cited by 236
“Recent kinase inhibitor specificity studies led the authors to recommend the parallel use of LiCl and kenpaullone for identifying the role of GSK3β in physiological processes (Bain et al., 2003).”
Mayer, C., & Belsham, D. D. (2009) · Endocrinology · doi:10.1210/en.2009-1122 · Cited by 241
“a range of kinases and enzymes and at the concentration used should be selective for JNK, although it has been reported to inhibit other protein kinases in vitro (41, 42).”
BackgroundChibalin, A. V., Leng, Y., Vieira, E., Krook, A., Björnholm, M., Long, Y. C., Kotova, O., Zhong, Z., Sakane, F., Steiler, T., et al. (2008) · Cell · doi:10.1016/j.cell.2007.12.035 · Cited by 232
Cdk5 Phosphorylation of Doublecortin Ser297 Regulates Its Effect on Neuronal Migration
Tanaka, T., Serneo, F. F., Tseng, H.-C., Kulkarni, A. B., Tsai, L., & Gleeson, J. G. (2004) · Neuron · doi:10.1016/s0896-6273(03)00852-3 · Cited by 241
Cell-Based Proteome Profiling of Potential Dasatinib Targets by Use of Affinity-Based Probes
Shi, H., Zhang, C., Chen, G. Y. J., & Yao, S. Q. (2012) · Journal of the American Chemical Society · doi:10.1021/ja208518u · Cited by 231
Metadata
- Authors
- BAIN, J., McLAUCHLAN, H., ELLIOTT, M., & COHEN, P.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- BAIN, Jenny
- McLAUCHLAN, Hilary
- ELLIOTT, Matthew
- COHEN, Philip
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2003-04-01
- Volume
- 371
- Issue
- 1
- Pages
- 199-204
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1223271
- OpenAlex
- W2011588737
- Cited by
- 1,369
- References
- 42
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 12 · 2023: 16 · 2022: 26 · 2021: 35 · 2020: 28 · 2019: 38 · 2018: 42 · 2017: 48 · 2016: 42 · 2015: 44 · 2014: 52 · 2013: 66 · 2012: 70
- FWCI
- 43.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
- Keywords
- protein kinase inhibitors, kinase selectivity, serine/threonine kinase, indirubin-3'-monoxime, KT5823, ML-9, kenpaullone, roscovitine, pyrazolopyrimidines, cyclin-dependent kinases, glycogen synthase kinase-3, Src family kinases, epigallocatechin gallate, DYRK1A, kinase substrate identification
- MeSH terms
- Alkaloids, Anthracenes, Azepines, Benzazepines, Carbazoles, Catechin, Enzyme Inhibitors, Indoles, Kinetin, Naphthalenes, Oximes, Purines, Pyrazoles, Pyrimidines, Substrate Specificity, Signal Transduction, Cyclin-Dependent Kinases, src-Family Kinases, Mitogen-Activated Protein Kinases, Glycogen Synthase Kinase 3, Protein Kinase Inhibitors, JNK Mitogen-Activated Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
