产品描述:
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).{24213,24248} 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).{24213} It inhibits phosphorylation of Akt at Thr308 and p70 ribosomal S6 kinase 1 (p70S6K1) at Thr389 in PC3 prostate cancer cells (IC50 = 300 nM).{24213} BX-795 (1 µM) also inhibits the secretion of IFN-β induced by LPS or poly(I:C) in RAW 264.7 macrophages.{24248} 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.{24247}