Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2.
- Resource Type
- Academic Journal
- Authors
- Kwiatkowski J; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Liu B; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Pang S; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Ahmad NHB; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Wang G; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Poulsen A; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Yang H; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Poh YR; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Tee DHY; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Ong E; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Retna P; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Dinie N; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Kwek P; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Wee JLK; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Manoharan V; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Low CB; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Seah PG; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Pendharkar V; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Sangthongpitag K; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Joy J; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Baburajendran N; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Jansson AE; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Nacro K; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Hill J; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Keller TH; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.; Hung AW; Experimental Drug Development Centre, Agency for Science, Technology and Research (ASTAR) , 10 Biopolis Way, Chromos #05-01/06 , 138670 Singapore.
- Source
- Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
- Subject
- Language
- English
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.