AG-879

Protein tyrosine kinase (PTK) inhibitors are potential antiproliferative agents for diseases caused by the hyperactivity of PTKs. Tyrphostins are a class of antiproliferative compounds which selectively inhibit PTKs of key growth factors.¹ AG-879 is a tyrphostin compound that inhibits nerve growth factor (NGF)-dependent TrkA tyrosine phosphorylation in PC-12 cells (IC₅₀ = ~40 μM), HER2-ErbB2 kinase in several breast and ovarian cancer cell lines (IC₅₀ = ~0.5 μM), and the VEGF receptor FLK1 (IC₅₀ = ~1 μM).² Additionally, AG-879 inhibits the activation of ETK with an IC₅₀ value of ~5 nM, which blocks tyrosine phosphorylation of PAK1, suppressing Ras transformation of NIH 3T3 fibroblasts.³ AG-879 has also been shown to suppress IL-6-induced tyrosine phosphorylation of STAT3 (IC₅₀ = 15 μM) in schwannoma cells.⁴

WARNING This product is not for human or veterinary use.

1. Gazit, A., Yaish, P., Gilon, C., et al. Tyrphostins I: Synthesis and biological activity of protein tyrosine kinase inhibitors. J. Med. Chem. 32(10), 2344-2352 (1989).

2. Levitzki, A., and Gazit, A. Tyrosine kinase inhibition: An approach to drug development. Science 267(5205), 1782-1788 (1995).

3. He, H., Hiokawa, Y., Gazit, A., et al. The tyr-kinase inhibitor AG879, that blocks the ETK-PAK1 interaction, suppresses the RAS-induced PAK1 activation and malignant transformation. Cancer Biol. Ther. 3(1), 96-101 (2004).

4. Lee, H.K., Seo, I.A., Lee, S.H., et al. Tyrphostin ErbB2 inhibitors AG825 and AG879 have non-specific suppressive effects on gp130/ STAT3 signaling. Korean J. Physiol. Pharmacol. 12(5), 281-286 (2008).