6JLR

Crystal structure of wild type MNK2 in complex with inhibitor

6JLR の概要

• エントリーDOI: 10.2210/pdb6jlr/pdb
• 分子名称: MAP kinase-interacting serine/threonine-protein kinase 2, 4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]benzamide (2 entities in total)
• 機能のキーワード: kinase, phosphorylation, inhibitor, mnk, kinase domain, transferase, cancer, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35940.81

構造登録者

Baburajendran, N.,Hill, J. (登録日: 2019-03-06, 公開日: 2020-02-12, 最終更新日: 2023-11-22)

主引用文献

Kwiatkowski, J.,Liu, B.,Pang, S.,Ahmad, N.H.B.,Wang, G.,Poulsen, A.,Yang, H.,Poh, Y.R.,Tee, D.H.Y.,Ong, E.,Retna, P.,Dinie, N.,Kwek, P.,Wee, J.L.K.,Manoharan, V.,Low, C.B.,Seah, P.G.,Pendharkar, V.,Sangthongpitag, K.,Joy, J.,Baburajendran, N.,Jansson, A.E.,Nacro, K.,Hill, J.,Keller, T.H.,Hung, A.W.
Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2.
J.Med.Chem., 63:621-637, 2020

PubMed 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.

PubMed: 31910010
DOI: 10.1021/acs.jmedchem.9b01582

実験手法

X-RAY DIFFRACTION (2.901 Å)