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...

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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
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author 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
author_facet 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
author_sort Agarwal, Sameer
collection PubMed
description 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.
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spelling pubmed-78345992021-01-26 Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor 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 Bioorg Med Chem Lett Article 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. Elsevier Ltd. 2020-11-01 2020-09-24 /pmc/articles/PMC7834599/ /pubmed/32980515 http://dx.doi.org/10.1016/j.bmcl.2020.127571 Text en © 2020 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
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
Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor
title Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor
title_full Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor
title_fullStr Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor
title_full_unstemmed Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor
title_short Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor
title_sort identification of a novel orally bioavailable nlrp3 inflammasome inhibitor
topic Article
url 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
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