The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors
Open accessAbstract
The recent discovery of the role of receptor interacting protein 1 (RIP1) kinase in tumor necrosis factor (TNF)-mediated inflammation has led to its emergence as a highly promising target for the treatment of multiple inflammatory diseases. We screened RIP1 against GSK's DNA-encoded small-molecule libraries and identified a novel highly potent benzoxazepinone inhibitor series. We demonstrate that this template possesses complete monokinase selectivity for RIP1 plus unique species selectivity for primate versus nonprimate RIP1. We elucidate the conformation of RIP1 bound to this benzoxazepinone inhibitor driving its high kinase selectivity and design specific mutations in murine RIP1 to restore potency to levels similar to primate RIP1. This series differentiates itself from known RIP1 inhibitors in combining high potency and kinase selectivity with good pharmacokinetic profiles in rodents. The favorable developability profile of this benzoxazepinone template, as exemplified by compound 14 (GSK'481), makes it an excellent starting point for further optimization into a RIP1 clinical candidate.
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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
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214
Necroptosis and its role in inflammation
Pasparakis, M., & Vandenabeele, P. (2015) · Nature · doi:10.1038/nature14191 · Cited by 2,148
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
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
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Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases
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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
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
DNA-encoded chemistry: enabling the deeper sampling of chemical space
Goodnow, R. A., Dumelin, C. E., & Keefe, A. D. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.213 · Cited by 621
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Metadata
- Authors
- Harris, P. A., King, B. W., Bandyopadhyay, D., Berger, S. B., Campobasso, N., Capriotti, C. A., Cox, J. A., Dare, L., Dong, X., Finger, J. N., Grady, L. C., Hoffman, S. J., Jeong, J. U., Kang, J., Kasparcova, V., Lakdawala, A. S., Lehr, R., McNulty, D. E., Nagilla, R., Ouellette, M. T., Pao, C. S., Rendina, A. R., Schaeffer, M. C., Summerfield, J. D., Swift, B. A., Totoritis, R. D., Ward, P., Zhang, A., Zhang, D., Marquis, R. W., Bertin, J., & Gough, P. J.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-02-23
- Volume
- 59
- Issue
- 5
- Pages
- 2163-2178
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2280294408
- Cited by
- 274
- References
- 5
- FWCI
- 24.71
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors. https://app.cochat.ai/papers/10.1021/acs.jmedchem.5b01898
- The paper
- Harris, P. A., King, B. W., Bandyopadhyay, D., Berger, S. B., Campobasso, N., Capriotti, C. A., Cox, J. A., Dare, L., Dong, X., Finger, J. N., Grady, L. C., Hoffman, S. J., Jeong, J. U., Kang, J., Kasparcova, V., Lakdawala, A. S., Lehr, R., McNulty, D. E., Nagilla, R., . . . Gough, P. J. (2016). DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.5b01898
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
