4UZD

SAR156497 an exquisitely selective inhibitor of Aurora kinases

4UZD の概要

• エントリーDOI: 10.2210/pdb4uzd/pdb
• 関連するPDBエントリー: 4UZH
• 分子名称: AURORA KINASE A, ethyl (9S)-9-[3-(1H-benzimidazol-2-yloxy)phenyl]-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylate (2 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: 2
• 化学式量合計: 67593.39

構造登録者

Pouzieux, S.,Delarbre, L.,Crenne, J.Y. (登録日: 2014-09-05, 公開日: 2014-11-19, 最終更新日: 2024-05-08)

主引用文献

Carry, J.C.,Clerc, F.F.,Minoux, H.,Schio, L.,Mauger, J.,Nair, A.,Parmantier, E.,Le Moigne, R.,Delorme, C.,Nicolas, J.P.,Krick, A.,Abecassis, P.Y.,Crocq-Stuerga, V.,Pouzieux, S.,Delarbre, L.,Maignan, S.,Bertrand, T.,Bjergarde, K.,Ma, N.,Lachaud, S.,Guizani, H.,Lebel, R.,Doerflinger, G.,Monget, S.,Perron, S.,Gasse, F.,Angouillant-Boniface, O.,Filoche-Romme, B.J.,Murer, M.,Gontier, S.,Prevost, C.,Monteiro, M.L.,Combeau, C.
Sar156497 an Exquisitely Selective Inhibitor of Aurora Kinases.
J.Med.Chem., 58:362-, 2015

PubMed Abstract: The Aurora family of serine/threonine kinases is essential for mitosis. Their crucial role in cell cycle regulation and aberrant expression in a broad range of malignancies have been demonstrated and have prompted intensive search for small molecule Aurora inhibitors. Indeed, over 10 of them have reached the clinic as potential anticancer therapies. We report herein the discovery and optimization of a novel series of tricyclic molecules that has led to SAR156497, an exquisitely selective Aurora A, B, and C inhibitor with in vitro and in vivo efficacy. We also provide insights into its mode of binding to its target proteins, which could explain its selectivity.

PubMed: 25369539
DOI: 10.1021/JM501326K

実験手法

X-RAY DIFFRACTION (3.2 Å)