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Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Kwiatkowski J,Liu B,Pang S,Ahmad NHB,Wang G,Poulsen A,Yang H,Poh YR,Tee DHY,Ong E,Retna P,Dinie N,Kwek P,Wee JLK,Manoharan V,Low CB,Seah PG,Pendharkar V,Sangthongpitag K,Joy J,Baburajendran N,Jansson AE,Nacro

doi

10.1021/acs.jmedchem.9b01582

subject

Has Abstract

pub_date

2020-01-23 00:00:00

pages

621-637

issue

2

eissn

0022-2623

issn

1520-4804

journal_volume

63

pub_type

杂志文章

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