PDB 4MQ1 deposited: 2013-09-15 modified: 2013-12-18
Title The crystal structure of DYRK1a with a bound pyrido[2,3-d]pyrimidine inhibitor
Authors Anderson, K., Chen, Y., Chen, Z., Dominique, R., Glenn, K., He, Y., Janson, C., Lukacs, C., Luk, K.C., Polonskaia, A., Qiao, Q., Railkar, A., Rossman, P., Sun, H., Vilenchik, M., Wovkulich, P., Xiang, Q., Zhang, X.
Structure factors resolution 2.35 rfactor 0.20178 rfree 0.24582
DPI 0.61 theoretical min: 0.30
Related PDB Entries 4MQ2

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.

Bioorg.Med.Chem.Lett. 2013 Dec; 23(24):6610-6615 doi:10.1016/j.bmcl.2013.10.055

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL3091386
PubMed 24239188 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
4MQ1/1 4MQ1 1 monomer 0 1 5 2787
4MQ1/2 4MQ1 2 monomer 0 1 5 2644
4MQ1/3 4MQ1 3 monomer 0 1 4 2471
4MQ1/4 4MQ1 4 monomer 0 1 4 2477