CGP 57380 (MNK1 Inhibitor) 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.

MNK1:2.2 μM

CGP57380 以约 3 μM 的 IC50 在体外抑制 eIF4E 的磷酸化。CGP57380 导致 eIF4E 脱磷酸化，并在 293 细胞中进一步增加帽依赖性报告。[1] CGP57380 导致剂量依赖性减少 Ang II 激活的 eIF4E 磷酸化、蛋白质合成和 VSMC 肥大。[2] CGP57380 使野生型细胞对小鼠胚胎成纤维细胞 (MEFs) 中血清撤离诱导的凋亡更加敏感。[3] CGP57380 阻止 BC 祖细胞的连续重复培养功能。[4]

CGP57380（40 mg/kg/d i.p.）有效地消除了BC CML细胞连续移植免疫缺陷小鼠以及作为LSCs的能力。[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.