5LXD

Crystal structure of DYRK2 in complex with EHT 1610 (compound 2)

Summary for 5LXD

• Entry DOI: 10.2210/pdb5lxd/pdb
• Descriptor: Dual specificity tyrosine-phosphorylation-regulated kinase 2, methyl 9-[(2-fluoranyl-4-methoxy-phenyl)amino]-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transferase, kinase, inhibitor, unusual binding mode, structural genomics, structural genomics consortium, sgc
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q92630
• Total number of polymer chains: 2
• Total formula weight: 95326.06

Authors

Chaikuad, A.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.,Bountra, C.,Besson, T.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2016-09-20, release date: 2016-10-26, Last modification date: 2024-11-06)

Primary citation

Chaikuad, A.,Diharce, J.,Schroder, M.,Foucourt, A.,Leblond, B.,Casagrande, A.S.,Desire, L.,Bonnet, P.,Knapp, S.,Besson, T.
An Unusual Binding Model of the Methyl 9-Anilinothiazolo[5,4-f] quinazoline-2-carbimidates (EHT 1610 and EHT 5372) Confers High Selectivity for Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases.
J. Med. Chem., 59:10315-10321, 2016

PubMed Abstract: Methyl 9-anilinothiazolo[5,4-f]quinazoline-2-carbimidates 1 (EHT 5372) and 2 (EHT 1610) are strong inhibitors of DYRK's family kinases. The crystal structures of the complex revealed a noncanonical binding mode of compounds 1 and 2 in DYRK2, explaining the remarkable selectivity and potency of these inhibitors. The structural data and comparison presented here provide therefore a template for further improvement of this inhibitor class and for the development of novel inhibitors selectively targeting DYRK kinases.

PubMed: 27766861
DOI: 10.1021/acs.jmedchem.6b01083

Experimental method

X-RAY DIFFRACTION (2.58 Å)