3ZTX

Aurora kinase selective inhibitors identified using a Taxol-induced checkpoint sensitivity screen.

3ZTX の概要

• エントリーDOI: 10.2210/pdb3ztx/pdb
• 関連するPDBエントリー: 2BFX 2BFY 2VGO 2VGP 2VRX
• 分子名称: 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)
• 機能のキーワード: transferase-cell cycle complex, transferase, taxol-induced checkpoint inhibitor, transferase/cell cycle
• 由来する生物種: XENOPUS LAEVIS; 詳細
• 細胞内の位置: Nucleus: Q6DE08; Chromosome, centromere: O13024
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 78084.26

構造登録者

Kwiatkowski, N.,Villa, F.,Musacchio, A.,Gray, N. (登録日: 2011-07-12, 公開日: 2012-02-01, 最終更新日: 2024-11-13)

主引用文献

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

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: 21992004
DOI: 10.1021/CB200305U

実験手法

X-RAY DIFFRACTION (1.95 Å)