生物活性

• 靶点

  MEK5 IC50:1.5nM

  ERK5 IC50:59nM

• 描述MEK5 is a dual specificity protein kinase that belongs to the mitogen-activated protein kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. BIX-02189 is a selective inhibitor of MEK5 with IC50 value of 1.5nM. BIX-02189 also inhibits ERK5, TGFβR1, ABL1, CSF1R, JAK3, KIT, LCK, MAPK14, RPS6KA3,RPS6KA6 and SRC with IC50 values of 59nM, 580nM, 2400nM, 46nM, 1000nM, 440nM, 1100nM, 250nM, 3700nM, 2100nM, 990nM and 7600nM, respectively. In vitro, BIX-02189 inhibited Hela and HEK293cells with IC50 values of 0.53nM and 0.26nM, respectively^[3]. Treatment A549 lung cancer cells with 2.5-10μM BIX-02189 completely hindered the EGF-induced phosphorylation of ERK5 in a concentration-dependent manner without affecting the phosphorylation of ERK1/2. BIX02189 significantly abolished TGF-β1-mediated E-cadherin repression and N-cadherin induction. In addition, BIX02189 inhibited TGF-β1-induced cell motility and activation of MMP-2 in A549 lung cancer cells. In vivo, Intraperitoneal administration of BIX-02189 at 20mg/kg once daily for 3 weeks inhibited TGF-β receptor type I (TβRI) derived lung metastasis in TβRI-derived A549 xenograft mouse model^[4].
• 作用机制BIX-02189 inhibits catalytic function of MEK5 and blocks phosphorylation of ERK. ^[5].