CGP 57380

CGP 57380 is a cell-permeable pyrazolo-pyrimidine compound that acts as a selective inhibitor of Mnk1 with IC₅₀ of 2.2 μM, but has no inhibitory activity against p38, JNK1, ERK1/2, PKC, or Src-like kinases. In Vitro: 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^[1]. CGP57380 results in dose-dependent decreases in Ang II-stimulated phosphorylation of eIF4E, protein synthesis, and VSMC hypertrophy^[2]. CGP57380 sensitizes wild-type cells for serum-withdrawal induced apoptosis in mouse embryo fibroblasts (MEFs)^[3]. CGP57380 prevents the serial replating function of BC progenitors^[4]. In Vivo: CGP57380 (40 mg/kg/d i.p.) potently extinguishes the ability of BC CML cells to serially transplant-immunodeficient mice and function as LSCs^[4].