3K5U
Identification, SAR Studies and X-ray Cocrystal Analysis of a Novel Furano-pyrimidine Aurora Kinase A Inhibitor
Summary for 3K5U
| Entry DOI | 10.2210/pdb3k5u/pdb |
| Descriptor | Serine/threonine-protein kinase 6, 2-[(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHANOL (3 entities in total) |
| Functional Keywords | aurora kinase inhibitors, virtual screening, x-ray co-crystal analysis, structure-based drug design (sbdd), h-bonding, atp-binding site, cell cycle, cytoskeleton, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : O14965 |
| Total number of polymer chains | 1 |
| Total formula weight | 32690.49 |
| Authors | Wu, J.S.,Leou, J.S.,Coumar, M.S.,Hsieh, H.P.,Wu, S.Y. (deposition date: 2009-10-08, release date: 2010-10-13, Last modification date: 2023-11-01) |
| Primary citation | Coumar, M.S.,Tsai, M.T.,Chu, C.Y.,Uang, B.J.,Lin, W.H.,Chang, C.Y.,Chang, T.Y.,Leou, J.S.,Teng, C.H.,Wu, J.S.,Fang, M.Y.,Chen, C.H.,Hsu, J.T.,Wu, S.Y.,Chao, Y.S.,Hsieh, H.P. Identification, SAR studies, and X-ray co-crystallographic analysis of a novel furanopyrimidine aurora kinase A inhibitor Chemmedchem, 5:255-267, 2010 Cited by PubMed Abstract: Herein we reveal a simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in-house compound library to select compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in-house compound library collection prior to testing. Five new series of Aurora kinase inhibitors were identified through this strategy, with IC(50) values ranging from approximately 300 nM to approximately 15 microM, by testing only 133 compounds from a database of approximately 125,000 compounds. Structure-activity relationship studies and X-ray co-crystallographic analysis of the most potent compound, a furanopyrimidine derivative with an IC(50) value of 309 nM toward Aurora kinase A, were carried out. The knowledge gained through these studies could help in the future design of potent Aurora kinase inhibitors. PubMed: 20039358DOI: 10.1002/cmdc.200900339 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.35 Å) |
Structure validation
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