6JLR

Crystal structure of wild type MNK2 in complex with inhibitor

Summary for 6JLR

• Entry DOI: 10.2210/pdb6jlr/pdb
• Descriptor: MAP kinase-interacting serine/threonine-protein kinase 2, 4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]benzamide (2 entities in total)
• Functional Keywords: kinase, phosphorylation, inhibitor, mnk, kinase domain, transferase, cancer, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 35940.81

Authors

Baburajendran, N.,Hill, J. (deposition date: 2019-03-06, release date: 2020-02-12, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.901 Å)