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Chemical Structure| 1849590-01-7 同义名 : eFT508
CAS号 : 1849590-01-7
货号 : A129059
分子式 : C17H20N6O2
纯度 : 99%+
分子量 : 340.38
MDL号 : MFCD30489732
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 3 mg/mL(8.81 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • MNK2

    MNK2, IC50:1 nM

  • MNK1

    MNK1, IC50:2.4 nM
描述 Mitogen-activated protein kinase interacting kinases (MNK) 1/2 are key regulators of mRNA translation integrating signals from oncogenic and immune signaling pathways through phosphorylation of eIF4E and other mRNA binding proteins. eFT508 Is a potent Inhibitor of MNK1 and MNK2 signaling and tumor growth. In all cell lines tested, eFT508 inhibited Ser209 phosphorylation of eIF4E with IC50 values ranging from 1.4 to 22 nM. This effect of eFT508 on eIF4E Ser209 phosphorylation is specific to MNK1/2 inhibition. Treatment of TMD8 cells for 48 h with eFT508 led to a dose-dependent reduction in secreted IL-6, IL-8, and TNFα. Taken together, eFT508 potently inhibited eIF4E phosphorylation, select mRNA stability, and pro-inflammatory cytokineproduction in DLBCL cells. eFT508 was well-tolerated at doses of 1 and 10 mg/kg QD as measured by lack of body weight loss, which corresponds to aminimal therapeutic index of≥10 in a TMD8 xenograft model. Furthermore, eFT508 treatment produced significant tumor growth inhibition (TGI) over a 10-fold dose range, achieving an average TGI of 71% and 75% when dosed orally at 1 and 10 mg/kg QD, respectively[2].
作用机制 eFT508 makes H-bond interactions with both hinge residues, Lys161 and Met162. The pyridone methyl interacts with the face of Phe159, and the Cys225 sulfur makes a Dunitz interaction[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.94mL

0.59mL

0.29mL

14.69mL

2.94mL

1.47mL

29.38mL

5.88mL

2.94mL
参考文献

[1]Kevin R, Vikas K, eFT508, a Potent and Selective Mitogen-Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 Inhibitor, Is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma (DLBCL). Blood 2015 126:1554

[2]Reich SH, Sprengeler PA, Chiang GG, et al. Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition. J Med Chem. 2018;61(8):3516-3540.