3P9J

Aurora A kinase domain with phthalazinone pyrazole inhibitor

3P9J の概要

• エントリーDOI: 10.2210/pdb3p9j/pdb
• 分子名称: Serine/threonine-protein kinase 6, 4-[(5-methyl-1H-pyrazol-3-yl)amino]-2-phenylphthalazin-1(2H)-one (3 entities in total)
• 機能のキーワード: phosphotransferase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31365.07

構造登録者

Kairies, N.A.,Oliveira, T.,Engh, R.A. (登録日: 2010-10-17, 公開日: 2011-03-23, 最終更新日: 2024-02-21)

主引用文献

Prime, M.E.,Courtney, S.M.,Brookfield, F.A.,Marston, R.W.,Walker, V.,Warne, J.,Boyd, A.E.,Kairies, N.A.,von der Saal, W.,Limberg, A.,Georges, G.,Engh, R.A.,Goller, B.,Rueger, P.,Rueth, M.
Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of aurora-a kinase.
J.Med.Chem., 54:312-319, 2011

PubMed Abstract: The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature. We report a novel class of Aurora kinase inhibitors based upon a phthalazinone pyrazole scaffold. The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680.

PubMed: 21128645
DOI: 10.1021/jm101346r

実験手法

X-RAY DIFFRACTION (2.8 Å)