3K5U

Identification, SAR Studies and X-ray Cocrystal Analysis of a Novel Furano-pyrimidine Aurora Kinase A Inhibitor

3K5U の概要

• エントリーDOI: 10.2210/pdb3k5u/pdb
• 分子名称: Serine/threonine-protein kinase 6, 2-[(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHANOL (3 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : O14965
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32690.49

構造登録者

Wu, J.S.,Leou, J.S.,Coumar, M.S.,Hsieh, H.P.,Wu, S.Y. (登録日: 2009-10-08, 公開日: 2010-10-13, 最終更新日: 2023-11-01)

主引用文献

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

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: 20039358
DOI: 10.1002/cmdc.200900339

実験手法

X-RAY DIFFRACTION (2.35 Å)