The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases
Open accessAbstract
RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.
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Cites
Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., & Yuan, J. (2005) · Nature Chemical Biology · doi:10.1038/nchembio711 · Cited by 3,068
Identification of RIP1 kinase as a specific cellular target of necrostatins
Degterev, A., Hitomi, J., Germscheid, M., Ch'en, I. L., Korkina, O., Teng, X., Abbott, D., Cuny, G. D., Yuan, C., Wagner, G., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.83 · Cited by 2,059
FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
Welz, P.-S., Wullaert, A., Vlantis, K., Kondylis, V., Fernández-Majada, V., Ermolaeva, M., Kirsch, P., Sterner-Kock, A., van Loo, G., & Pasparakis, M. (2011) · Nature · doi:10.1038/nature10273 · Cited by 594
Necroptosis: A Specialized Pathway of Programmed Necrosis
Galluzzi, L., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2008.12.004 · Cited by 561
RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis
Dannappel, M., Vlantis, K., Kumari, S., Polykratis, A., Kim, C., Wachsmuth, L., Eftychi, C., Lin, J., Corona, T., Hermance, N., et al. (2014) · Nature · doi:10.1038/nature13608 · Cited by 534
Berger, S. B., Kasparcova, V., Hoffman, S., Swift, B., Dare, L., Schaeffer, M., Capriotti, C., Cook, M., Finger, J., Hughes-Earle, A., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400499 · Cited by 374
Self-citationTRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation
Jouan-Lanhouet, S., Arshad, M. I., Piquet-Pellorce, C., Martin-Chouly, C., Le Moigne-Muller, G., Van Herreweghe, F., Takahashi, N., Sergent, O., Lagadic-Gossmann, D., Vandenabeele, P., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.90 · Cited by 357
RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis
Takahashi, N., Vereecke, L., Bertrand, M. J. M., Duprez, L., Berger, S. B., Divert, T., Gonçalves, A., Sze, M., Gilbert, B., Kourula, S., et al. (2014) · Nature · doi:10.1038/nature13706 · Cited by 318
Self-citationBonnet, M. C., Preukschat, D., Welz, P.-S., van Loo, G., Ermolaeva, M. A., Bloch, W., Haase, I., & Pasparakis, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.08.014 · Cited by 295
Research works printed but not linked: 22
- 10.1038/nature10400 · DOI · Paper page
- 10.1016/j.ceb.2009.12.003 · DOI · Paper page
- 10.1038/cddis.2012.64 · DOI · Paper page
- 10.1016/j.immuni.2014.12.031 · DOI · Paper page
- 10.1016/j.immuni.2016.06.007 · DOI · Paper page
- 10.1097/SHK.0b013e31820b2db1 · DOI
- 10.1016/j.str.2013.01.016 · DOI · Paper page
- 10.1038/cddis.2012.64 · DOI · Paper page
- 10.1016/j.bmcl.2005.07.077 · DOI · Paper page
- 10.1021/ml400382p · DOI
- 10.1038/cddiscovery.2015.9 · DOI
- 10.1038/nchembio.211 · DOI · Paper page
- 10.1021/acs.jmedchem.5b01898 · DOI · Paper page
- 10.1021/ac961242d · DOI · Paper page
- 10.1021/ja506518t · doi:10.1021/ja506518t
- 10.1002/9780470559277.ch130145 · DOI
- 10.1039/c2md20111a · DOI · Paper page
- Katritzky A. R., 2010, Handbook of Heterocyclic Chemistry, 149
- 10.1038/nchembio.1938 · DOI · Paper page
- 10.1126/science.1098231 · DOI · Paper page
- 10.1053/j.gastro.2014.03.049 · DOI
- 10.1016/j.immuni.2011.09.020 · DOI · Paper page
Cited by
Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases
Yuan, J., Amin, P., & Ofengeim, D. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0093-1 · Cited by 967
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009
Tong, X., Tang, R., Xiao, M., Xu, J., Wang, W., Zhang, B., Liu, J., Yu, X., & Shi, S. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01392-3 · Cited by 883
Expanding the medicinal chemistry synthetic toolbox
Boström, J., Brown, D. G., Young, R. J., & Keserü, G. M. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.116 · Cited by 665
Kinase inhibition in autoimmunity and inflammation
Zarrin, A. A., Bao, K., Lupardus, P., & Vucic, D. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0082-8 · Cited by 431
Metadata
- Authors
- Harris, P. A., Berger, S. B., Jeong, J. U., Nagilla, R., Bandyopadhyay, D., Campobasso, N., Capriotti, C. A., Cox, J. A., Dare, L., Dong, X., Eidam, P. M., Finger, J. N., Hoffman, S. J., Kang, J., Kasparcova, V., King, B. W., Lehr, R., Lan, Y., Leister, L. K., Lich, J. D., MacDonald, T. T., Miller, N. A., Ouellette, M. T., Pao, C. S., Rahman, A., Reilly, M. A., Rendina, A. R., Rivera, E. J., Schaeffer, M. C., Sehon, C. A., Singhaus, R. R., Sun, H. H., Swift, B. A., Totoritis, R. D., Vossenkämper, A., Ward, P., Wisnoski, D. D., Zhang, D., Marquis, R. W., Gough, P. J., & Bertin, J.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-02-10
- Volume
- 60
- Issue
- 4
- Pages
- 1247-1261
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2584580415
- Cited by
- 480
- References
- 9
- FWCI
- 14.85
- Type
- journal article
- Language
- en
- Open access
- green
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- Harris, P. A., Berger, S. B., Jeong, J. U., Nagilla, R., Bandyopadhyay, D., Campobasso, N., Capriotti, C. A., Cox, J. A., Dare, L., Dong, X., Eidam, P. M., Finger, J. N., Hoffman, S. J., Kang, J., Kasparcova, V., King, B. W., Lehr, R., Lan, Y., Leister, L. K., . . . Bertin, J. (2017). Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.6b01751
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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