title: Identification of Inhibitors of NOD1-Induced Nuclear Factor-κB Activation.
abstract: NOD1 (nucleotide-binding oligomerization domain 1) protein is a member of the NLR (NACHT and leucine rich repeat domain containing proteins) protein family, which plays a key role in innate immunity as a sensor of specific microbial components derived from bacterial peptidoglycans and induction of inflammatory responses. Mutations in NOD proteins have been associated with various inflammatory diseases that affect NF-κB (nuclear factor κB) activity, a major signaling pathway involved in apoptosis, inflammation, and immune response. A luciferase-based reporter gene assay was utilized in a high-throughput screening program conducted under the NIH-sponsored Molecular Libraries Probe Production Center Network program to identify the active scaffolds. Herein, we report the chemical synthesis, structure-activity relationship studies, downstream counterscreens, secondary assay data, and pharmacological profiling of the 2-aminobenzimidazole lead (compound 1c, ML130) as a potent and selective inhibitor of NOD1-induced NF-κB activation.
authors: Pasha M
authors: PM
authors: Khan
authors: Ricardo G
authors: RG
authors: Correa
authors: Daniela B
authors: DB
authors: Divlianska
authors: Satyamaheshwar
authors: S
authors: Peddibhotla
authors: E Hampton
authors: EH
authors: Sessions
authors: Gavin
authors: G
authors: Magnuson
authors: Brock
authors: B
authors: Brown
authors: Eigo
authors: E
authors: Suyama
authors: Hongbin
authors: H
authors: Yuan
authors: Arianna
authors: A
authors: Mangravita-Novo
authors: Michael
authors: M
authors: Vicchiarelli
authors: Ying
authors: Y
authors: Su
authors: Stefan
authors: S
authors: Vasile
authors: Layton H
authors: LH
authors: Smith
authors: Paul W
authors: PW
authors: Diaz
authors: John C
authors: JC
authors: Reed
authors: Gregory P
authors: GP
authors: Roth