The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Discovery of Potent and Selective Covalent Inhibitors of JNK
Open accessAbstract
The mitogen activated kinases JNK1/2/3 are key enzymes in signaling modules that transduce and integrate extracellular stimuli into coordinated cellular response. Here we report the discovery of the first irreversible inhibitors of JNK1/2/3. We describe two JNK3 co-crystal structures at 2.60 and 2.97 Å resolutions that show the compounds form covalent bonds with a conserved cysteine residue. JNK-IN-8 is a selective JNK inhibitor that inhibits phosphorylation of c-Jun, a direct substrate of JNK kinase, in cells exposed to sub-micromolar drug in a manner that depends on covalent modification of the conserved cysteine residue. Extensive biochemical, cellular and pathway-based profiling establish the selectivity of JNK-IN-8 for JNK and suggest that the compound will be broadly useful as a pharmacological probe of JNK-dependent signal transduction. Potential lead compounds have also been identified for kinases including IRAK1, PIK3C3, PIP4K2C, and PIP5K3.
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Cites
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
A central role for JNK in obesity and insulin resistance
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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 · cited 2×
“For example, one of the earliest and still most widely used inhibitors is the anthrapyrazolone, SP-600125 (Bennett et al., 2001; Figure 1A), which exhibits exceptionally low specificity for JNK (Bain et al., 2007) and should only be used in combination with other tools to rule out a potential role…”
MethodA 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
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BackgroundNovel mutant-selective EGFR kinase inhibitors against EGFR T790M
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The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901
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Cited by
Jackson, P. A., Widen, J. C., Harki, D. A., & Brummond, K. M. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00788 · Cited by 588
Targeted Covalent Inhibitors for Drug Design
Baillie, T. A. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201601091 · Cited by 578
Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors
Zhang, T., Kwiatkowski, N., Olson, C. M., Dixon-Clarke, S. E., Abraham, B. J., Greifenberg, A. K., Ficarro, S. B., Elkins, J. M., Liang, Y., Hannett, N. M., et al. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2166 · Cited by 374
Self-citationDual or multi-targeting inhibitors: The next generation anticancer agents
Raghavendra, N. M., Pingili, D., Kadasi, S., Mettu, A., & Prasad, S. V. U. M. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.021 · Cited by 333
Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening
Resnick, E., Bradley, A., Gan, J., Douangamath, A., Krojer, T., Sethi, R., Geurink, P. P., Aimon, A., Amitai, G., Bellini, D., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b02822 · Cited by 335
Metadata
- Authors
- Zhang, T., Inesta-Vaquera, F., Niepel, M., Zhang, J., Ficarro, S. B., Machleidt, T., Xie, T., Marto, J. A., Kim, N., Sim, T., Laughlin, J. D., Park, H., LoGrasso, P. V., Patricelli, M., Nomanbhoy, T. K., Sorger, P. K., Alessi, D. R., & Gray, N. S.
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 19
- Issue
- 1
- Pages
- 140-154
- ISSN
- 1074-5521 (ISSN-L)
- OpenAlex
- W2170444099
- Cited by
- 349
- References
- 13
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Zhang, T., Inesta-Vaquera, F., Niepel, M., Zhang, J., Ficarro, S. B., Machleidt, T., Xie, T., Marto, J. A., Kim, N., Sim, T., Laughlin, J. D., Park, H., LoGrasso, P. V., Patricelli, M., Nomanbhoy, T. K., Sorger, P. K., Alessi, D. R., & Gray, N. S. (2012). Discovery of Potent and Selective Covalent Inhibitors of JNK. Chemistry & Biology. https://doi.org/10.1016/j.chembiol.2011.11.010
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