GNE-2861 is an inhibitor of the group 2 p21-activated kinases (PAKs; IC50s = 7.5, 126, and 36 nM for PAK4, -5, and -6, respectively).1 It is selective for group 2 PAKs over group 1 PAKs (IC50s = 5.42, 0.97, and >10 μM for PAK1, -2, and -3, respectively), as well as JAK3, KHS1, MAP4K4, and MINK1 at 1 μM. GNE-2861 (0.1-50 μM) inhibits cell migration and reduces cell viability of MDA-MB-436 and MCF-10A PIK3CA cells in a concentration-dependent manner. It sensitizes drug-resistant MCF-7/LCC2 breast cancer cells to tamoxifen .2
1.Staben, S.T., Feng, J.A., Lyle, K., et al.Back pocket flexibility provides group II p21-activated kinase (PAK) selectivity for type I 1/2 kinase inhibitorsJ. Med. Chem.57(3)1033-1045(2014) 2.Zhuang, T., Zhu, J., Li, Z., et al.p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer cellsOncotarget6(41)43853-43868(2015)