3THB

Structure of PLK1 kinase domain in complex with a benzolactam-derived inhibitor

3THB の概要

• エントリーDOI: 10.2210/pdb3thb/pdb
• 分子名称: Serine/threonine-protein kinase PLK1, ZINC ION, 9-chloro-2-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thi one (3 entities in total)
• 機能のキーワード: kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P53350
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37999.03

構造登録者

Sintchak, M.D. (登録日: 2011-08-18, 公開日: 2011-11-23, 最終更新日: 2023-09-13)

主引用文献

Duffey, M.O.,Vos, T.J.,Adams, R.,Alley, J.,Anthony, J.,Barrett, C.,Bharathan, I.,Bowman, D.,Bump, N.J.,Chau, R.,Cullis, C.,Driscoll, D.L.,Elder, A.,Forsyth, N.,Frazer, J.,Guo, J.,Guo, L.,Hyer, M.L.,Janowick, D.,Kulkarni, B.,Lai, S.J.,Lasky, K.,Li, G.,Li, J.,Liao, D.,Little, J.,Peng, B.,Qian, M.G.,Reynolds, D.J.,Rezaei, M.,Scott, M.P.,Sells, T.B.,Shinde, V.,Shi, Q.J.,Sintchak, M.D.,Soucy, F.,Sprott, K.T.,Stroud, S.G.,Nestor, M.,Visiers, I.,Weatherhead, G.,Ye, Y.,D'Amore, N.
Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905).
J.Med.Chem., 55:197-208, 2012

PubMed Abstract: This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

PubMed: 22070629
DOI: 10.1021/jm2011172

実験手法

X-RAY DIFFRACTION (2.5 Å)