3ZTX
Aurora kinase selective inhibitors identified using a Taxol-induced checkpoint sensitivity screen.
Summary for 3ZTX
| Entry DOI | 10.2210/pdb3ztx/pdb |
| Related | 2BFX 2BFY 2VGO 2VGP 2VRX |
| Descriptor | SERINE/THREONINE-PROTEIN KINASE 12-A, INNER CENTROMERE PROTEIN A, 2-((4-(4-HYDROXYPIPERIDIN-1-YL)PHENYL)AMINO)-5,11-DIMETHYL-5H-BENZO[E]PYRIMIDO [5,4-B][1,4]DIAZEPIN-6(11H)-ONE, ... (4 entities in total) |
| Functional Keywords | transferase-cell cycle complex, transferase, taxol-induced checkpoint inhibitor, transferase/cell cycle |
| Biological source | XENOPUS LAEVIS More |
| Cellular location | Nucleus: Q6DE08 Chromosome, centromere: O13024 |
| Total number of polymer chains | 4 |
| Total formula weight | 78084.26 |
| Authors | Kwiatkowski, N.,Villa, F.,Musacchio, A.,Gray, N. (deposition date: 2011-07-12, release date: 2012-02-01, Last modification date: 2024-11-13) |
| Primary citation | Kwiatkowski, N.,Deng, X.,Wang, J.,Tan, L.,Villa, F.,Santaguida, S.,Huang, H.C.,Mitchison, T.,Musacchio, A.,Gray, N. Selective Aurora Kinase Inhibitors Identified Using a Taxol- Induced Checkpoint Sensitivity Screen. Acs Chem.Biol., 7:185-, 2012 Cited by PubMed Abstract: The members of the Aurora kinase family play critical roles in the regulation of the cell cycle and mitotic spindle assembly and have been intensively investigated as potential targets for a new class of anticancer drugs. We describe a new highly potent and selective class of Aurora kinase inhibitors discovered using a phenotypic cellular screen. Optimized inhibitors display many of the hallmarks of Aurora inhibition including endoreduplication, polyploidy, and loss of cell viability in cancer cells. Structure-activity relationships with respect to kinome-wide selectivity and guided by an Aurora B co-crystal structure resulted in the identification of key selectivity determinants and discovery of a subseries with selectivity toward Aurora A. A direct comparison of biochemical and cellular profiles with respect to published Aurora inhibitors including VX-680, AZD1152, MLN8054, and a pyrimidine-based compound from Genentech demonstrates that compounds 1 and 3 will become valuable additional pharmacological probes of Aurora-dependent functions. PubMed: 21992004DOI: 10.1021/CB200305U PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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