4DHF

Structure of Aurora A mutant bound to Biogenidec cpd 15

4DHF の概要

• エントリーDOI: 10.2210/pdb4dhf/pdb
• 関連するPDBエントリー: 3R21 3R22
• 分子名称: Aurora kinase A, 7-cyclopentyl-2-({1-methyl-5-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-3-yl}amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: ser/thr kinase mitotic kinase pyrazolopyrimidine, phosphorylation, tpx2, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, centrosome: O14965
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63833.50

構造登録者

Silvian, L.,Marcotte, D.J. (登録日: 2012-01-27, 公開日: 2012-07-18, 最終更新日: 2024-02-28)

主引用文献

Le Brazidec, J.Y.,Pasis, A.,Tam, B.,Boykin, C.,Wang, D.,Marcotte, D.J.,Claassen, G.,Chong, J.H.,Chao, J.,Fan, J.,Nguyen, K.,Silvian, L.,Ling, L.,Zhang, L.,Choi, M.,Teng, M.,Pathan, N.,Zhao, S.,Li, T.,Taveras, A.
Structure-based design of 2,6,7-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines as Aurora kinases inhibitors.
Bioorg.Med.Chem.Lett., 22:4033-4037, 2012

PubMed Abstract: This Letter reports the optimization of a pyrrolopyrimidine series as dual inhibitors of Aurora A/B kinases. This series derived from a pyrazolopyrimidine series previously reported as inhibitors of aurora kinases and CDKs. In an effort to improve the selectivity of this chemotype, we switched to the pyrrolopyrimidine core which allowed functionalization on C-2. In addition, the modeling rationale was based on superimposing the structures of Aurora-A kinase and CDK2 which revealed enough differences leading to a path for selectivity improvement. The synthesis of the new series of pyrrolopyrimidine analogs relied on the development of a different route for the two key intermediates 7 and 19 which led to analogs with both tunable activity against CDK1 and maintained cell potency.

PubMed: 22607669
DOI: 10.1016/j.bmcl.2012.04.085

実験手法

X-RAY DIFFRACTION (2.8 Å)