| Literature DB >> 31910010 |
Jacek Kwiatkowski1, Boping Liu1, Shermaine Pang1, Nur Huda Binte Ahmad1, Gang Wang1, Anders Poulsen1, Haiyan Yang1, Yong Rui Poh1, Doris Hui Ying Tee1, Esther Ong1, Priya Retna1, Nurul Dinie1, Perlyn Kwek1, John Liang Kuan Wee1, Vithya Manoharan1, Choon Bing Low1, Peck Gee Seah1, Vishal Pendharkar1, Kanda Sangthongpitag1, Joma Joy1, Nithya Baburajendran1, Anna Elisabet Jansson1, Kassoum Nacro1, Jeffrey Hill1, Thomas H Keller1, Alvin W Hung1.
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.Entities:
Year: 2020 PMID： 31910010 DOI： 10.1021/acs.jmedchem.9b01582
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446