The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation
Open accessAbstract
Significance: The NLRP3 inflammasome is an intracellular oligomer regulating the activation of caspase-1 for the processing and secretion of IL-1β and IL-18. Although there is growing evidence to substantiate inflammasome inhibition as a therapeutic option for the treatment of inflammatory diseases, to date, there are no approved humans agents. OLT1177, a β-sulfonyl nitrile molecule, shown to be safe in humans, is a selective inhibitor of the NLRP3 inflammasome, with unique properties to reverse the metabolic costs of inflammation and to treat IL-1β– and IL-18–mediated diseases.
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Cites
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Succinate is an inflammatory signal that induces IL-1β through HIF-1α
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“Indeed, succinate levels correlate with the stabilization of HIF-1 α and the induction of proinflammatory cascades leading to the accumulation and release of IL-1 β (44).”
BackgroundNLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
Inflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
Coll, R. C., Robertson, A. A. B., Chae, J. J., Higgins, S. C., Muñoz-Planillo, R., Inserra, M. C., Vetter, I., Dungan, L. S., Monks, B. G., Stutz, A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3806 · Cited by 2,849
Inflammatory caspases are innate immune receptors for intracellular LPS
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The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease
Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3804 · Cited by 2,172
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Cited by
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884
Targeting the NLRP3 inflammasome in inflammatory diseases
Mangan, M. S. J., Olhava, E. J., Roush, W. R., Seidel, H. M., Glick, G. D., & Latz, E. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.97 · Cited by 1,885
Inflammasomes in neuroinflammatory and neurodegenerative diseases
Voet, S., Srinivasan, S., Lamkanfi, M., & van Loo, G. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810248 · Cited by 761
Pharmacological Inhibitors of the NLRP3 Inflammasome
Zahid, A., Li, B., Kombe, A. J. K., Jin, T., & Tao, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02538 · Cited by 671
Blevins, H. M., Xu, Y., Biby, S., & Zhang, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.879021 · Cited by 587
Metadata
- Authors
- Marchetti, C., Swartzwelter, B., Gamboni, F., Neff, C. P., Richter, K., Azam, T., Carta, S., Tengesdal, I., Nemkov, T., D’Alessandro, A., Henry, C., Jones, G. S., Goodrich, S. A., St. Laurent, J. P., Jones, T. M., Scribner, C. L., Barrow, R. B., Altman, R. D., Skouras, D. B., Gattorno, M., Grau, V., Janciauskiene, S., Rubartelli, A., Joosten, L. A. B., & Dinarello, C. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2018-01-29
- Volume
- 115
- Issue
- 7
- Pages
- E1530-E1539
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2791711864
- Cited by
- 574
- References
- 45
- FWCI
- 13.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. https://app.cochat.ai/papers/10.1073/pnas.1716095115
- The paper
- Marchetti, C., Swartzwelter, B., Gamboni, F., Neff, C. P., Richter, K., Azam, T., Carta, S., Tengesdal, I., Nemkov, T., D’Alessandro, A., Henry, C., Jones, G. S., Goodrich, S. A., St. Laurent, J. P., Jones, T. M., Scribner, C. L., Barrow, R. B., Altman, R. D., Skouras, D. B., . . . Dinarello, C. A. (2018). OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1716095115
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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.
