Kodiak’s novel small molecule NLRP3 inhibitor candidates decrease IL - 1 β production and reduce inflammasome complex formation in preclinical studies 23 ! " # ! " $ ! B ! & ! ' $ E $ " $ $ " E $ ) * ) + , - . L M + 1 2 3 ) 4 3 R 3 S + T 2 8 9 : ; 2 < 3 1 ) * = ! " # $ % C ' E ! " # $ % C ' F ! " # $ % C ' G + , , - . L Inhibitors directly affect NLRP3 molecular interactions † ! " # ! " $ ! % ! & ! ' $ ( $ " $ $ " ( $ ) ! * + I - . L ! " M L 1 2 - 3 4 5 3 S 3 7 1 U - 9 : ; < - = 7 3 [ ? ] A 7 3 1 4 ! " # A B C D ( ! " # A B C D ) ! " # A B C D * ! " # A B C D + , * * - . L NLRP3 inhibitors decrease macrophage IL - 1 β production in multiple human macrophage lines* * U937 cells were treated with NLRP3 inhibitors and nigericin activation to monitor IL - 1b production † Compounds dose - dependently displace a small molecule tracer that promotes the inactivate conformation of NLRP3 in cells NLRP3 inhibitors reduce inflammasome complex formation • NLRP3 inhibitors, but not the anti - inflammatory steroid dexamethasone, decreased detectable fusion protein complexes NLRP3 inhibitor https://kodiak.com/wp - content/uploads/sites/4/2024/05/22. - 2024 - ARVO - NLRP3 - Cell - Assays.pdf Kodiak Sciences. Investigative Ophthalmology & Visual Science June 2024, Vol.65, 2208. THP - 1 cells expressing GFP - ASC fusion protein were differentiated, primed, compound treated and activated (green)
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