| In Vitro | In vitro activity: CGP57380 inhibits phosphorylation of eIF4E in cellular assays with IC50 of about 3 μM. CGP57380 causes dephosphorylation of eIF4E, and induces a further increase in the cap-dependent reporter in 293 cells. CGP57380 results in dose-dependent decreases in Ang II-stimulated phosphorylation of eIF4E, protein synthesis, and VSMC hypertrophy. CGP57380 sensitizes wild-type cells for serum-withdrawal induced apoptosis in mouse embryo fibroblasts (MEFs). CGP57380 prevents the serial replating function of BC progenitors.
Kinase Assay: CGP 57380 is potent inhibitor of MNK1 with IC50 value of 2.2 μM.
Cell Assay: In 293 cells, CGP 57380 (10 μM) inhibited eIF4E phosphorylation in response to fetal calf serum (FCS), arsenite, anisomycin, PMA or tumor necrosis factor alpha. Also, CGP 57380 increased the cap-dependent reporter rluc. In cellular assays, CGP 57380 inhibited eIF4E phosphorylation with IC50 value of 3 μM. In rat vascular smooth muscle cells, CGP 57380 inhibited eIF4E phosphorylation, protein synthesis and VSMC hypertrophy induced by angiotensin II in a dose dependent way. In mouse macrophages, CGP 57380 concentration-dependently inhibited TNFα production stimulated by Escherichia coli lipopolysaccharide (LPS) through posttranscriptional regulation. In bone marrow-derived macrophages, CGP 57380 significantly inhibited the production of proinflammatory cytokines monocyte chemoattractant protein-1, TNF and IL-6. |
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