BX-795

BX-795 is a multi-kinase inhibitor that is an ATP-competitive inhibitor of 3-phosphoinositide-dependent protein kinase 1 (PDK1) and TANK-binding kinase 1 (TBK1; IC₅₀s = 6 and 11 nM, respectively).^1,2 It also inhibits the CAMK family kinases AMPK-related kinase 5 (NUAK1; IC₅₀ = 5 nM) and microtubule affinity-regulating kinase 1 (MARK1), MARK2, MARK3, and MARK4 (IC₅₀s = 55, 53, 81, and 19 nM, respectively), as well as the MAP3K kinases mixed-lineages kinase 1 (MLK1), MLK2, and MLK3 (IC₅₀s = 50, 46, and 42 nM, respectively). BX-795 is selective for these kinases over five additional kinases (IC₅₀s = >1,100 nM) but does inhibit the receptor tyrosine kinase VEGFR, as well as IκB kinase ε (IΚΚε) and Aurora B kinase (IC₅₀s = 41 and 31 nM, respectively).¹ It inhibits phosphorylation of Akt at Thr³⁰⁸ and p70 ribosomal S6 kinase 1 (p70S6K1) at Thr³⁸⁹ in PC3 prostate cancer cells (IC₅₀ = 300 nM).¹ BX-795 (1 µM) also inhibits the secretion of IFN-β induced by LPS or poly(I:C) in RAW 264.7 macrophages.² It inhibits the proliferation of PC3 prostate and MDA-MB-468 breast cancer cells (IC₅₀s = 250 and 720 nM, respectively). BX-795 (5 µM) inhibits the proliferation of PDK1^-/- murine embryonic stem cells expressing either wild-type PDK1 or PDK1 with an alanine-to-glycine (L159G) mutation.³

WARNING This product is not for human or veterinary use.

1. Feldman, R.I., Wu, J.M., Polokoff, M.A., et al. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. The Journal of Biological Chemisty 280(20), 19867-19874 (2005).

2. Clark, K., Plater, L., Peggie, M., et al. Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IκB kinase ε: A distinct upstream kinase mediates Ser-172 phosphorylation and activation. The Journal of Biological Chemisty 284(21), 14136-14146 (2009).

3. Tamgüney, T., Zhang, C., Fiedler, D., et al. Analysis of 3-phosphoinositide-dependent kinase-1 signaling and function in ES cells. Exp. Cell Res. 314(11-12), 2299-2312 (2008).