A pan-Pim kinase inhibitor
The family of Pim (Provirus Integration site for Moloney murine leukemia virus) proteins are serine/threonine kinases involved in cell survival and cell proliferation. CX-6258 is a potent, reversible inhibitor of Pim-1, -2, and -3 (IC50s = 5, 25, and 16 nM, respectively).1 It demonstrates excellent selectivity, inhibiting only FLT3 from a panel of 107 additional kinases. CX-6258 dose-dependently blocks the phosphorylation of the Pim targets Bad, 4E-BP1, and NKX3.1.1,2 It acts synergistically with the chemotherapeutics doxorubicin and paclitaxel, presumably because CX-6258 impairs Pim-mediated enhanced expression of P-glycoprotein.1 CX-6258 is orally bioavailable and inhibits the growth of MV4-11 xenografts in mice.1
1.Haddach, M., Michaux, J., Schwaebe, M.K., et al.Discovery of CX-6258. A potent, selective, and orally efficacious pan-Pim kinases inhibitorACS Med. Chem. Lett.3(2)135-139(2011) 2.Padmanabhan, A., Gosc, E.B., and Bieberich, C.J.Stabilization of the prostate-specific tumor suppressor NKX3.1 by the oncogenic protein kinase Pim-1 in prostate cancer cellsJ. Cell. Biochem.1141050-1057(2013)
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