TAPI-2

The extracellular domains of many different types of transmembrane proteins, including growth factors, growth factor receptors and cell adhesion molecules, are proteolytically released (shed) in response to environmental cues. TNF protease inhibitor 2 (TAPI-2) is a broad-spectrum inhibitor of TNF-α converting enzyme (TACE), other ADAMs (a disintegrin and metalloproteinases), and other matrix metalloproteinases. It inhibits phorbol-12-myristate-13-acetate-induced (PMA) shedding of various cell surface proteins, such as TGF-α, β amyloid precursor protein, L-selectin, and IL-6 receptor α subunit, with an IC₅₀ value of 10 µM.¹ TAPI-2 inhibits ADAM8, 10, 12, and TACE with K_i values of 10, 3, 100, and 0.12 µM, respectively.² In T4-2 breast cancer cells, 20 µM TAPI-2 prevented mobilization of the growth factors TGF-α and amphiregulin leading to reversion of the malignant cellular phenotype.³

WARNING This product is not for human or veterinary use.

1. Arribas, J., Coodly, L., Vollmer, P., et al. Diverse cell surface protein ectodomains are shed by a system sensitive to metalloprotease inhibitors. The Journal of Biological Chemisty 271(19), 11376-11386 (1996).

2. Moss, M.L., and Rasmussen, F.H. Fluorescent substrates for the proteinases ADAM17, ADAM10, ADAM8, and ADAM12 useful for high-throughput inhibitor screening. Anal. Biochem. 366(2), 144-148 (2007).

3. Kenny, P.A., and Bissell, M.J. Targeting TACE-dependent EGFR ligand shedding in breast cancer. J. Clin. Invest. 117(2), 337-345 (2007).