CAY10657

The NF-κB/Rel family of transcription factors induce and coordinate the expression of pro-inflammatory genes including cytokines, chemokines, interferons, MHC proteins, growth factors, and cell adhesion molecules. Under resting conditions NF-κB dimers are retained in the cytoplasm by a member of the IκB family of inhibitory proteins. Upon activation by cytokines or other stimuli, IKK phosphorylates IκB, initiating a signaling cascade to activate gene transcription.^1,2,3 CAY10657 is a thiophenecarboximide derivative proposed to inhibit IKK2.⁴ Currently, there are no published reports of its biological activity. However, inhibition of NF-κB activation is likely to be of broad utility in the treatment of inflammatory diseases and cancer.^5,6

WARNING This product is not for human or veterinary use.

1. Delhase, M., Hayakawa, M., Chen, Y., et al. Positive and negative regulation of IκB kinase activity through IKKβ subunit phophorylation. Science 284, 309-313 (1999).

2. Israël, A. The IKK complex: an integrator of all signals that activate NF-κB. Trends Cell Biol. 10, 129-133 (2000).

3. Mercurio, F., Zhu, H., Murray, B.W., et al. IKK-1 and IKK-2: Cytokine-activated IκB kinases essential for NF-κB activation. Science 278(5339), 860-866 (1997).

4. Faull, A., Johnstone, C., Morley, A., et al. Novel compounds. PCT/SE02/01403, 1-175 (2003).

5. Baxter, A., Brough, S., Cooper, A., et al. Hit-to-lead studies: The discovery of potent, orally active, thiophenecarboxamide IKK-2 inhibitors. Bioorg. Med. Chem. Lett. 14(11), 2817-2822 (2004).

6. Kishore, N., Sommers, C., Mathialagan, S., et al. A selective IKK-2 inhibitor blocks NF- kB-dependent gene expression in interleukin-1β-stimulated synovial fibroblasts. The Journal of Biological Chemisty 278(35), 32861-32871 (2003).