Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor

NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases, including COVID-19. In this study, rationally designed alkenyl sulfonylurea derivatives were identified as novel, potent and orally bioavailable NLRP3 inhibitors. Compound 7 was found to be potent...

Descripción completa

Detalles Bibliográficos
Autores principales: Agarwal, Sameer, Pethani, Jignesh P., Shah, Hardik A., Vyas, Vismit, Sasane, Santosh, Bhavsar, Harsh, Bandyopadhyay, Debdutta, Giri, Poonam, Viswanathan, Kasinath, Jain, Mukul R., Sharma, Rajiv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834599/
https://www.ncbi.nlm.nih.gov/pubmed/32980515
http://dx.doi.org/10.1016/j.bmcl.2020.127571
Descripción
Sumario:NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases, including COVID-19. In this study, rationally designed alkenyl sulfonylurea derivatives were identified as novel, potent and orally bioavailable NLRP3 inhibitors. Compound 7 was found to be potent (IL-1β IC(50) = 35 nM; IL-18 IC(50) = 33 nM) and selective NLRP3 inflammasome inhibitor with excellent pharmacokinetic profile having oral bioavailability of 99% in mice.

Ejemplares similares