4EEH

Hsp90 Alpha N-terminal Domain in Complex with an Inhibitor 3-(4-Hydroxy-phenyl)-1H-indazol-6-ol

4EEH の概要

• エントリーDOI: 10.2210/pdb4eeh/pdb
• 関連するPDBエントリー: 3B28 4EFT 4EFU
• 分子名称: Heat shock protein HSP 90-alpha, 3-(4-hydroxyphenyl)-1H-indazol-6-ol, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: atp binding, chaperone-chaperone inhibitor complex, chaperone/chaperone inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P07900
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26036.12

構造登録者

Musil, D.,Lehmann, M.,Graedler, U.,Buchstaller, H.-P. (登録日: 2012-03-28, 公開日: 2012-06-27, 最終更新日: 2024-03-20)

主引用文献

Buchstaller, H.-P.,Eggenweiler, H.-M.,Sirrenberg, C.,Graedler, U.,Musil, D.,Hoppe, E.,Zimmermann, A.,Schwartz, H.,Maerz, J.,Bomke, J.,Wegener, A.,Wolf, M.
Fragment-based discovery of hydroxy-indazole-carboxamides as novel small molecule inhibitors of Hsp90
Bioorg.Med.Chem.Lett., 22:4396-4403, 2012

PubMed Abstract: Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential molecular therapeutic agents for the treatment of cancer. Here we describe the identification of novel small molecular weight inhibitors of Hsp90 using a fragment based approach. Fragments were selected by docking, tested in a biochemical assay and the confirmed hits were crystallized. Information gained from X-ray structures of these fragments and other chemotypes was used to drive the fragment evolution process. Optimization of these high μM binders resulted in 3-benzylindazole derivatives with significantly improved affinity and anti-proliferative effects in different human cancer cell lines.

PubMed: 22632933
DOI: 10.1016/j.bmcl.2012.04.121

実験手法

X-RAY DIFFRACTION (1.6 Å)