4A4L

CRYSTAL STRUCTURE OF POLO-LIKE KINASE 1 IN COMPLEX WITH A 5-(2-AMINO- PYRIMIDIN-4-YL)-1H-PYRROLE INHIBITOR

4A4L の概要

• エントリーDOI: 10.2210/pdb4a4l/pdb
• 関連するPDBエントリー: 1Q4K 1Q4O 1UMW 2V5Q 2YAC 4A4O
• 分子名称: SERINE/THREONINE-PROTEIN KINASE PLK1, ZINC ION, L(+)-TARTARIC ACID, ... (5 entities in total)
• 機能のキーワード: transferase
• 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: 36337.49

構造登録者

Bertrand, J.A.,Bossi, R.T. (登録日: 2011-10-17, 公開日: 2012-01-11, 最終更新日: 2024-05-01)

主引用文献

Caruso, M.,Valsasina, B.,Ballinari, D.,Bertrand, J.A.,Brasca, M.G.,Caldarelli, M.,Cappella, P.,Fiorentini, F.,Gianellini, L.M.,Scolaro, A.,Beria, I.
5-(2-Amino-Pyrimidin-4-Yl)-1H-Pyrrole and 2-(2-Amino-Pyrimidin-4-Yl)-1,5,6,7-Tetrahydro-Pyrrolo[3,2-C]Pyridin-4-One Derivatives as New Classes of Selective and Orally Available Polo-Like Kinase 1 Inhibitors.
Bioorg.Med.Chem.Lett., 22:96-, 2012

PubMed Abstract: The discovery and characterization of two new chemical classes of potent and selective Polo-like kinase 1 (PLK1) inhibitors is reported. For the most interesting compounds, we discuss the biological activities, crystal structures and preliminary pharmacokinetic parameters. The more advanced compounds inhibit PLK1 in the enzymatic assay at the nM level and exhibit good activity in cell proliferation on A2780 cells. Furthermore, these compounds showed high levels of selectivity on a panel of unrelated kinases, as well as against PLK2 and PLK3 isoforms. Additionally, the compounds show acceptable oral bioavailability in mice making these inhibitors suitable candidates for further in vivo activity studies.

PubMed: 22154349
DOI: 10.1016/J.BMCL.2011.11.065

実験手法

X-RAY DIFFRACTION (2.35 Å)