A new IkappaB kinase beta inhibitor prevents human breast cancer progression through negative regulation of cell cycle transition.

Constitutive nuclear factor-kappaB (NF-kappaB) activity plays a crucial role in the development and progression of lymphoma, leukemia, and some epithelial cancers. Given the contribution of NF-kappaB in carcinogenesis, a novel approach that interferes with its activity might have therapeutic potential against cancers that respond poorly to conventional treatments. Here, we have shown that a new IkappaB kinase beta inhibitor, IMD-0354, suppressed the growth of human breast cancer cells, MDA-MB-231, HMC1-8, and MCF-7, by arresting cell cycle and inducing apoptosis.

A novel NF-kappaB inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors.

Constitutive phosphorylation of c-kit tyrosine kinase is the major cause of factor-independent proliferation of mast cells. Recently available tyrosine kinase inhibitors have shown marked activity against mast cell lines that carry wild-type c-kit, and some, but not others, carry mutant c-kit. Here we clearly demonstrated that a novel NF-kappaB inhibitor, IMD-0354, restrained factor-independent proliferation of mast cells with c-kit mutations but not of normal mast cells.