BMS-345541 Is a Highly Selective Inhibitor of IκB Kinase That Binds at an Allosteric Site of the Enzyme and Blocks NF-κB-dependent Transcription in Mice

Direct role of NF‐κB activation in Toll‐like receptor‐triggered HLA‐DRA expression

“…4D). To substantiate the requirement for NF-jB activation in the transcriptional up-regulation of HLA-DRA following TLR triggering by CpG-DNA and LPS, we tested the effect of BMS-345541, an IjB kinase-2 (IKK-2) inhibitor [27] on the expression of HLA-DRA mRNA. Fig.…”

Bim and Noxa Are Candidates to Mediate the Deleterious Effect of the NF-κB Subunit RelA in Cerebral Ischemia

“…Previous work has shown that NF-B is activated in cerebral ischemia by the IKK complex. BMS-345541, a specific IKK inhibitor (Burke et al, 2003), protected against ischemic brain damage . IKK activity is reflected by the phosphorylation state of IKK.…”

Inhibitors of NF-κB signaling: 785 and counting

“…ATP analogs include natural products such as b-carboline, and several synthetic compounds developed by pharmaceutical companies, such as SC-839, which has an approximately 200-fold preference for IKKb as compared to IKKa (reviewed in Karin et al, 2004;Pande and Ramos, 2005). On the other hand, the synthetic compound BMS-345541 binds to an allosteric site on both kinases, but shows an approximately 10-fold greater inhibitory effect on IKKb (Burke et al, 2003). Several thiol-reactive compounds, such as parthenolide, certain epoxyquinoids and arsenite, have been shown to block IKKb activity through Cys-179 (Kapahi et al, 2000;Kwok et al, 2001;Liang et al, 2003Liang et al, , 2006, probably in most cases through a direct conjugation to the thiol group of this cysteine.…”