TAE684

Human anaplastic lymphoma kinase (ALK) is an oncogene that is amplified in neuroblastomas and when juxtaposed with various fusion partners, its constitutive kinase activity is associated with the development of a type of anaplastic large cell lymphoma (ALCL).^1,2 TAE684 is an ALK inhibitor that blocks the proliferation of ALCL-derived and ALK-dependent cell lines with IC₅₀ values of 2-5 nM.¹ When tested against a panel of 35 cells transformed by various tyrosine kinases, TAE684 demonstrated 100- to 1,000-fold selectivity for inhibiting ALK-driven cell proliferation.¹ TAE684 treatment induces cell cycle arrest and apoptosis in ALK-dependent cell lines and has been used to suppress tumor growth in in vivo models of ALK-positive ALCL and neuroblastoma.^1,2 TAE684 is also reported to inhibit the activity of the Parkinson’s disease-linked leucine-rich repeat kinase 2 (IC₅₀s = 7.8 and 6.1 nM for wild-type and G2019S mutant LRRK2, respectively).³

WARNING This product is not for human or veterinary use.

1. Galkin, A.V., Melnick, J.S., Kim, S., et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc. Natl. Acad. Sci. USA 104(1), 270-275 (2007).

2. Hasan, M.K., Nafady, A., Takatori, A., et al. ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma. Sci. Rep. 3, (2013).

3. Zhang, J., Deng, X., Choi, H.G., et al. Characterization of TAE684 as a potent LRRK2 kinase inhibitor. Bioorg. Med. Chem. Lett. 22(55), 1864-1869 (2012).