Publication: Development of an Acrylate Derivative Targeting the NLRP3 Inflam- masome for the Treatment of Inflammatory Bowel Disease
Authors
Cocco, Mattia ; Pellegrini, Carolina ; Martínez-Banaclocha, Helios ; Giorgis, Marta ; Marini, Elisabetta ; Costale, Annalisa ; Miglio, Gianluca ; Fornai, Matteo ; Antonioli, Luca ; López-Castejón, Gloria ; Angosto, Diego ; Hafner-Bratkovic, Iva ; Regazzoni, Luca ; Blandizzi, Corrado ; Bertinaria, Massimo ; Tapia Abellán, Ana ; Pelegrín Vivancos, Pablo
item.page.secondaryauthor
item.page.director
Publisher
ACS Publications
publication.page.editor
publication.page.department
DOI
10.1021/acs.jmedchem.6b01624
item.page.type
info:eu-repo/semantics/article
Description
©2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the Accepted, version of a Published Work that appeared in final form Journal of Medicinal Chemistry. To access the final edited and published work see 10.1021/acs.jmedchem.6b01624
Abstract
Pharmacological inhibition of NLRP3 inflammasome activation may offer a new option in the treatment of Inflamma- tory Bowel Disease (IBD). In this work, we report the design, the synthesis, and the biological screening of a series of acrylate derivatives as NLRP3 inhibitors. The in vitro determination of reactivity, cytotoxicity, NLRP3 ATPase inhibition, and antipyroptotic properties allowed the selection of 11 (INF39), a stable, non toxic compound inhibiting interleukin 1β release from macrophages. Bioluminescence resonance energy transfer experiments proved that this compound was able to directly interfere with NLRP3 acti- vation in cells. In vivo studies confirmed the ability of the selected lead to alleviate the effects of DNBS-induced colitis in rats after oral administration.
publication.page.subject
Citation
Journal of Medicinal Chemistry, volumen 60, nº 9, año 2017, páginas: 3656-3671
item.page.embargo
Collections
Ir a Estadísticas
Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/