IMD 0354

IMD 0354 is an IKKβ (IKK2) inhibitor that blocks NF-κB phosphorylation (IC₅₀ = ~250 nM) and subsequent NF-κB p65 nuclear translocation.¹ It exhibits cardioprotective properties by decreasing expression of P-selectin and ICAM-1 in the vasculature and blocking cardiomyocyte IL-1β and MCP-1 production, resulting in suppressed neutrophil accumulation in a rat model of ischemia/reperfusion injury.¹ IMD 0354, suppresses the growth of human breast cancer cells by inducing cell cycle arrest and apoptosis.² It induces apoptosis of chronic lymphocytic leukemia cells at 1-10 µM by directly targeting the NF-κB pathway, decreasing expression of anti-apoptotic genes and increasing expression of proapoptotic genes.³

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1. Onai, Y., Suzuki, J.i., Kakuta, T., et al. Inhibition of IκB phosphorylation in cardiomyocytes attenuates myocardial ischemia/reperfusion injury. Cardiovasc. Res. 63(1), 51-59 (2004).

2. Tanaka, A., Muto, S., Konno, M., et al. A new IκB kinase β inhibitor prevents human breast cancer progression through negative regulation of cell cycle transition. Cancer Res. 66(1), 419-426 (2006).

3. Kanduri, M., Tobin, G., Åleskog, A., et al. The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia. Blood Cancer J. 1(3), 1-6 (2011).