Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2.
Basic Information
ID: ALA4376877
Journal: J Med Chem
Title: Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2.
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 K, Hill J, Keller TH, Hung AW.
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.
CiteXplore: 31910010
DOI: 10.1021/acs.jmedchem.9b01582
Patent ID: ┄