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Título: | Development of nitroalkene-based inhibitors to target STING-dependent inflammation |
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 |
Tipo: | Artículo |
Palabras clave: | Stimulator of Interferon Genes, Drug discovery Nitroalkene-based compounds, STING inhibitors, STING-associated vasculopathy with onset in infancy, Interferon |
Fecha de publicación: | 2024 |
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 |
Editorial: | Elsevier |
EN: | Redox Biology, 2024, 74: 103202. |
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 |
ISSN: | 2213-2317 |
Licencia: | Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0) |
Aparece en las colecciones: | Publicaciones académicas y científicas - Facultad de Ciencias |
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