4MQ1

The crystal structure of DYRK1a with a bound pyrido[2,3-d]pyrimidine inhibitor

Summary for 4MQ1

• Entry DOI: 10.2210/pdb4mq1/pdb
• Related: 2vx3 4MQ2
• Descriptor: Dual specificity tyrosine-phosphorylation-regulated kinase 1A, N-(5-{[(1R)-3-amino-1-(3-chlorophenyl)propyl]carbamoyl}-2-chlorophenyl)-2-methoxy-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide, PENTAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: dyrk1a, dyrk1b, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus speckle: Q13627
• Total number of polymer chains: 4
• Total formula weight: 172689.86

Authors

Lukacs, C.M.,Janson, C.A.,Garvie, C.,Liang, L. (deposition date: 2013-09-15, release date: 2013-12-11, Last modification date: 2023-12-06)

Primary citation

Anderson, K.,Chen, Y.,Chen, Z.,Dominique, R.,Glenn, K.,He, Y.,Janson, C.,Luk, K.C.,Lukacs, C.,Polonskaia, A.,Qiao, Q.,Railkar, A.,Rossman, P.,Sun, H.,Xiang, Q.,Vilenchik, M.,Wovkulich, P.,Zhang, X.
Pyrido[2,3-d]pyrimidines: Discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors.
Bioorg.Med.Chem.Lett., 23:6610-6615, 2013

PubMed Abstract: DYRK1B is a kinase over-expressed in certain cancer cells (including colon, ovarian, pancreatic, etc.). Recent publications have demonstrated inhibition of DYRK1B could be an attractive target for cancer therapy. From a data-mining effort, the team has discovered analogues of pyrido[2,3-d]pyrimidines as potent enantio-selective inhibitors of DYRK1B. Cells treated with a tool compound from this series showed the same cellular effects as down regulation of DYRK1B with siRNA. Such effects are consistent with the proposed mechanism of action. Progress of the SAR study is presented.

PubMed: 24239188
DOI: 10.1016/j.bmcl.2013.10.055

Experimental method

X-RAY DIFFRACTION (2.35 Å)