The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Small-Molecule Inhibition of TNF-α
Abstract
We have identified a small-molecule inhibitor of tumor necrosis factor α (TNF-α) that promotes subunit disassembly of this trimeric cytokine family member. The compound inhibits TNF-α activity in biochemical and cell-based assays with median inhibitory concentrations of 22 and 4.6 micromolar, respectively. Formation of an intermediate complex between the compound and the intact trimer results in a 600-fold accelerated subunit dissociation rate that leads to trimer dissociation. A structure solved by x-ray crystallography reveals that a single compound molecule displaces a subunit of the trimer to form a complex with a dimer of TNF-α subunits.
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Self-citationAnti-TNF-α therapies: the next generation
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Cited by
Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality
Arkin, M. R., Tang, Y., & Wells, J. A. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.09.001 · Cited by 1,065
Regulation of tumour necrosis factor signalling: live or let die
Brenner, D., Blaser, H., & Mak, T. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3834 · Cited by 998
McCoy, M. K., & Tansey, M. G. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-45 · Cited by 847
Sedger, L. M., & McDermott, M. F. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.07.016 · Cited by 771
The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic
Broder, S. (2010) · Antiviral Research · doi:10.1016/j.antiviral.2009.10.002 · Cited by 520
Metadata
- Authors
- He, M. M., Smith, A. S., Oslob, J. D., Flanagan, W. M., Braisted, A. C., Whitty, A., Cancilla, M. T., Wang, J., Lugovskoy, A. A., Yoburn, J. C., Fung, A. D., Farrington, G., Eldredge, J. K., Day, E. S., Cruz, L. A., Cachero, T. G., Miller, S. K., Friedman, J. E., Choong, I. C., & Cunningham, B. C.
- Venue
- Science
- Published
- 2005-11-11
- Volume
- 310
- Issue
- 5750
- Pages
- 1022-1025
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2131847864
- Cited by
- 620
- References
- 13
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- closed
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- He, M. M., Smith, A. S., Oslob, J. D., Flanagan, W. M., Braisted, A. C., Whitty, A., Cancilla, M. T., Wang, J., Lugovskoy, A. A., Yoburn, J. C., Fung, A. D., Farrington, G., Eldredge, J. K., Day, E. S., Cruz, L. A., Cachero, T. G., Miller, S. K., Friedman, J. E., Choong, I. C., & Cunningham, B. C. (2005). Small-Molecule Inhibition of TNF-α. Science. https://doi.org/10.1126/science.1116304
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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.
