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Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor.

ABSTRACT: NLRP3 inflammasome mediated release of interleukin-1? (IL-1?) 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-1? IC₅₀ = 35 nM; IL-18 IC₅₀ = 33 nM) and selective NLRP3 inflammasome inhibitor with excellent pharmacokinetic profile having oral bioavailability of 99% in mice.

SUBMITTER: Agarwal S

PROVIDER: S-EPMC7834599 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor.

Agarwal Sameer S Pethani Jignesh P JP Shah Hardik A HA Vyas Vismit V Sasane Santosh S Bhavsar Harsh H Bandyopadhyay Debdutta D Giri Poonam P Viswanathan Kasinath K Jain Mukul R MR Sharma Rajiv R

Bioorganic & medicinal chemistry letters 20200924 21

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 IC50 = 35 nM; IL-18 IC50 = 33 nM) and selective NLRP3 inflammasome inhibitor with excellent pharmacokinetic profile having oral bioavailability of 99% in mice. ...[more]

PMID: 32980515

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