期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 63, 期 2, 页码 621-637出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.9b01582
关键词
-
资金
- Agency for Science, Technology and Research (A*STAR)
Dysregulation of translation initiation factor 4E (eIF4E) activity occurs in various cancers. Mitogen-activated protein kinase (MAPK) interacting kinases 1 and 2 (MNK1 and MNK2) play a fundamental role in activation of eIF4E. Structure-activity relationship-driven expansion of a fragment hit led to discovery of dual MNK1 and MNK2 inhibitors based on a novel pyridine-benzamide scaffold. The compounds possess promising in vitro and in vivo pharmacokinetic profiles and show potent on target inhibition of eIF4E phosphorylation in cells.
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