Summary
PDB 4MQ2 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.
Method X-RAY DIFFRACTION
Structure factors resolution 2.8 rfactor 0.18991 rfree 0.25754
DPI 0.97 theoretical min: 0.48
Related PDB Entries 4MQ1
Citations

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
4MQ2/1 4MQ2 1 monomer 0 1 5 2522
4MQ2/2 4MQ2 2 monomer 0 1 6 2488
4MQ2/3 4MQ2 3 monomer 0 1 2 2451
4MQ2/4 4MQ2 4 monomer 0 1 2 2356