Uses
SR12343, an IKK/NF-κB inhibitor, is a NF-κB essential modulator (NEMO)-binding domain (NBD) mimetic. SR12343 inhibits TNF-α- and LPS-induced NF-κB activation by blocking the interaction between IKKβ and NEMO, with an IC50 of 37.02 μM for TNF-α-mediated NF-κB activation. SR12343 suppresses LPS-induced acute pulmonary inflammation in mice. SR12343 can be used for research of inflammatory and degenerative diseases[1].
Biological Activity
SR 12343 is a mimetic of the IκB kinase β (IKKβ) NEMO/IKKγ-binding domain (NBD) that inhibits the protein-protein interaction between the IKK complex subunits NF-κB essential modulator (NEMO/IKKγ) and IKKβ.1 It selectively disrupts the association of NEMO/IKKγ with IKKβ over TNF receptor-associated factor 2 (TRAF2), IκBα, and IKKα in co-immunoprecipitation assays using RAW 264.7 cells at concentrations ranging from 25 to 150 μM. SR 12343 inhibits TNF-α-induced NF-κB activation in a reporter assay. It reduces increased serum IL-6 levels in a mouse model of LPS-induced endotoxemia when administered at a dose of 10 mg/kg. SR 12343 (30 mg/kg) improves grip strength and reduces muscle fibrosis in the mdx mouse model of Duchenne muscular dystrophy.
References
1.Zhao, J., Zhang, L., Mu, X., et al.Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-kB activationPLoS Biol.16(6)e2004663(2018)
