Título:
Development of nitroalkene-based inhibitors to target STING-dependent inflammation
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Autor:
Chang, Fei
Gunderstofte, Camila
Colussi, Nicole
Pitts, Mareena
Salvatore, S.R.
Thielke, Anne L.
Turell Novo, Lucía
Alvarez, Beatriz
Goldbach-Mansky, Raphaela
Villacorta, Luis
Holm, Christian K.
Schopfer, F.J.
Hansen, Anne Louise
Gunderstofte, Camila
Colussi, Nicole
Pitts, Mareena
Salvatore, S.R.
Thielke, Anne L.
Turell Novo, Lucía
Alvarez, Beatriz
Goldbach-Mansky, Raphaela
Villacorta, Luis
Holm, Christian K.
Schopfer, F.J.
Hansen, Anne Louise
Tutor:
Tipo de documento:
Artículo
Editor:
Palabras clave:
Stimulator of Interferon Genes
Drug discovery Nitroalkene-based compounds
STING inhibitors
STING-associated vasculopathy with onset in infancy
Interferon
Drug discovery Nitroalkene-based compounds
STING inhibitors
STING-associated vasculopathy with onset in infancy
Interferon
Descriptores:
Año de publicación:
2024
Contenido:
Resumen:
Stimulator of Interferon Genes (STING) is essential for the inflammatory response to cytosolic DNA. Despite that
aberrant activation of STING is linked to an increasing number of inflammatory diseases, the development of
inhibitors has been challenging, with no compounds in the pipeline beyond the preclinical stage. We previously
identified endogenous nitrated fatty acids as novel reversible STING inhibitors. With the aim of improving the
specificity and efficacy of these compounds, we developed and tested a library of nitroalkene-based compounds
for in vitro and in vivo STING inhibition. The structure-activity relationship study revealed a robustly improved
electrophilicity and reduced degrees of freedom of nitroalkenes by conjugation with an aromatic moiety. The
lead compounds CP-36 and CP-45, featuring a β-nitrostyrene moiety, potently inhibited STING activity in vitro
and relieved STING-dependent inflammation in vivo. This validates the potential for nitroalkene compounds as
drug candidates for STING modulation to treat STING-driven inflammatory diseases, providing new robust leads
for preclinical development.
Descripción:
Información suplementaria en: https://doi.org/10.1016/j.redox.2024.103202
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Editorial:
Elsevier
EN:
Redox Biology, 2024, 74: 103202.
Financiadores:
Citación:
Chang, F, Gunderstofte, C, Colussi, N [y otros autores]. "Development of nitroalkene-based inhibitors to target STING-dependent inflammation". Redox Biology. [en línea] 2024, 74: 103202. 14 h. DOI: 10.1016/j.redox.2024.103202
Citación:
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ISBN:
e-ISBN:
ISSN:
2213-2317
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Licencia:
Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)
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| Ficheros | Descripción | Tamaño | Formato | ||
|---|---|---|---|---|---|
| 10.1016-j.redox.2024.103202.pdf | — | 10.32 MB | Adobe PDF |