CGP 57380 是细胞渗透的吡唑-嘧啶类化合物，是一种具有选择性的MNK1抑制剂，IC50值为 2.2 μM。

CGP 57380 is a potent MNK1 inhibitor with IC50 of 2.2 μM, exhibiting no inhibitory activity on p38, JNK1, ERK1 and -2, PKC, or c-Src-like kinases.

CGP57380 inhibits phosphorylation of eIF4E in vitro 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]

CGP57380 (40 mg/kg/d i.p.) potently abrogates the ability of BC CML cells to serially transplant-immunodeficient mice and function as LSCs. [4]

Recombinant p38 isoforms are activated by Mkk6(E) under the following conditions: p38 (100 ng/mL), Mkk6(E) (30 ng/mL), ATP (100 mM) are mixed in kinase buffer (25 mM Hepes, 25 mM b-glycerophosphate, 0.1 mM sodium orthovanadate, 25 mM MgCl2, 2.5 mM DTT, pH 7.4) and incubated for 30 min at 30°C. A typical assay reaction for Mnk1 activity contained Mnk1 (2 ng/mL), HA-eIF4E (10 ng/mL), ATP (300 mM) in kinase buffer. The reaction is started by addition of activated p38 (0.03-3 ng/mL) and stopped after 30 min at 30°C by addition of SDS loading buffer. Inhibitors of Mnk1 are identified under the same assay conditions, except that Mnk1 is pre-activated using active p38a before exposure to the substrate and inhibitors.

522629-08-9

C11H9FN6

244.233

MNK1 Inhibitor;N3-(4-氟苯基)-1H-吡唑并[3,4-D]嘧啶-3,4-二胺

Ethanol:<1 mgml
H2O:<1 mgml
DMSO:45 mg/mL (184.3 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years