3MYG

Aurora A Kinase complexed with SCH 1473759

3MYG の概要

• エントリーDOI: 10.2210/pdb3myg/pdb
• 分子名称: Serine/threonine-protein kinase 6, TETRAETHYLENE GLYCOL, 2-{ethyl[(5-{[6-methyl-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]amino}isothiazol-3-yl)methyl]amino}-2-methylpropan-1-ol, ... (4 entities in total)
• 機能のキーワード: kinase, cell cycle, inhibitor, 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: 32060.91

構造登録者

Hruza, A.,Prosis, W.,Ramanathan, L. (登録日: 2010-05-10, 公開日: 2010-07-21, 最終更新日: 2023-09-06)

主引用文献

Yu, T.,Tagat, J.R.,Kerekes, A.D.,Doll, R.J.,Zhang, Y.,Xiao, Y.,Esposite, S.,Belanger, D.B.,Curran, P.J.,Mandal, A.K.,Siddiqui, M.A.,Shih, N.Y.,Basso, A.D.,Liu, M.,Gray, K.,Tevar, S.,Jones, J.,Lee, S.,Liang, L.,Ponery, S.,Smith, E.B.,Hruza, A.,Voigt, J.,Ramanathan, L.,Prosise, W.,Hu, M.
Discovery of a Potent, Injectable Inhibitor of Aurora Kinases Based on the Imidazo-[1,2-a]-Pyrazine Core.
ACS Med Chem Lett, 1:214-218, 2010

PubMed Abstract: The imidazo-[1,2-a]-pyrazine (1) is a dual inhibitor of Aurora kinases A and B with modest cell potency (IC50 = 250 nM) and low solubility (5 μM). Lead optimization guided by the binding mode led to the acyclic amino alcohol 12k (SCH 1473759), which is a picomolar inhibitor of Aurora kinases (TdF K d Aur A = 0.02 nM and Aur B = 0.03 nM) with improved cell potency (phos-HH3 inhibition IC50 = 25 nM) and intrinsic aqueous solubility (11.4 mM). It also demonstrated efficacy and target engagement in human tumor xenograft mouse models.

PubMed: 24900197
DOI: 10.1021/ml100063w

実験手法

X-RAY DIFFRACTION (2.4 Å)