BMS345541

BMS-345541 is a synthetic small-molecule inhibitor of the IκB kinase (IKK) complex, with activity focused on IKKβ. It is widely used as a chemical probe in cellular and biochemical studies to investigate the NF-κB signaling pathway. The compound is not a therapeutic agent; rather, it serves as a research tool to dissect the role of IKKβ in inflammatory responses and related cellular processes.

Mechanistically, BMS-345541 inhibits the kinase activity of IKKβ, which normally phosphorylates the inhibitor IκBα. Inhibition of IKKβ prevents IκBα phosphorylation and subsequent degradation, thereby stabilizing IκBα and blocking the translocation of NF-κB to the nucleus. This leads to reduced transcription of NF-κB target genes involved in inflammation, immune responses, cell survival, and proliferation.

In terms of selectivity and potency, BMS-345541 is considered a potent inhibitor of IKKβ in vitro and is often described as having greater activity against IKKβ than IKKα, enabling preferential suppression of NF-κB signaling through IKKβ. However, at higher concentrations or in certain contexts, some off-target effects can occur, and the compound’s activity can vary with assay conditions and cell type.

Applications of BMS-345541 include studying inflammatory and autoimmune mechanisms, cancer cell biology, apoptosis, and cytokine production. It is commonly employed in cell-based assays to confirm NF-κB–dependent phenotypes and is frequently used alongside genetic approaches to validate pathway involvement. Limitations include its status as a research tool rather than a clinically approved drug, potential off-target effects at non-ideal concentrations, and variability in pharmacokinetic or solubility properties that can affect in vivo use.

BMS-345541 is intended for research use and should be handled according to standard laboratory safety practices.