1XNN

CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN T877A MUTANT COMPLEX WITH (3A-ALPHA-,4-ALPHA 7-ALPHA-,7A-ALPHA-)-3A,4,7,7A-TETRAHYDRO-2-(4-NITRO-1-NAPHTHALENYL)-4,7-ETHANO-1H-ISOINDOLE-1,3(2H)-DIONE.

1XNN の概要

• エントリーDOI: 10.2210/pdb1xnn/pdb
• 分子名称: Androgen receptor, REL-(3AR,4S,7R,7AS)-3A,4,7,7A-TETRAHYDRO-2-(4-NITRO-1-NAPHTHALENYL)-4,7-ETHANO-1H-ISOINDOLE-1,3(2H)-DIONE (3 entities in total)
• 機能のキーワード: androgen receptor, steroid receptor, nuclear receptor, transcription regulation, ligand-binding domain, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Nucleus: P15207
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30602.76

構造登録者

Sack, J. (登録日: 2004-10-05, 公開日: 2005-10-11, 最終更新日: 2023-08-23)

主引用文献

Salvati, M.E.,Balog, A.,Shan, W.,Wei, D.D.,Pickering, D.,Attar, R.M.,Geng, J.,Rizzo, C.A.,Gottardis, M.M.,Weinmann, R.,Krystek, S.R.,Sack, J.,An, Y.,Kish, K.
Structure based approach to the design of bicyclic-1H-isoindole-1,3(2H)-dione based androgen receptor antagonists.
Bioorg.Med.Chem.Lett., 15:271-276, 2005

PubMed Abstract: A novel series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). Co-crystallization of members of this family of inhibitors was successfully accomplished with the T877A AR LBD. A working model of how this class of compounds functions to antagonize the AR was created. Based on this model, it was proposed that expanding the bicyclic portion of the molecule should result in analogs which function as effective antagonists against a variety of AR isoforms. In contrast to what was predicted by the model, SAR around this new series was dictated by the aniline portion rather than the bicyclic portion of the molecule.

PubMed: 15603938
DOI: 10.1016/j.bmcl.2004.10.085

実験手法

X-RAY DIFFRACTION (2.2 Å)