2YHD

Human androgen receptor in complex with AF2 small molecule inhibitor

2YHD の概要

• エントリーDOI: 10.2210/pdb2yhd/pdb
• 関連するPDBエントリー: 1E3G 1GS4 1T5Z 1T63 1T65 1XJ7 1XOW 1XQ3 1Z95 2AM9 2AMA 2AMB 2AO6 2AX6 2AX7 2AX8 2AX9 2AXA
• 分子名称: ANDROGEN RECEPTOR, SULFATE ION, TESTOSTERONE, ... (5 entities in total)
• 機能のキーワード: transcription, activation function 2 site (af2), small molecule inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus: P10275
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29708.87

構造登録者

AxerioCilies, P.,Lack, N.A.,ShashiNayana, M.R.,Chan, K.H.,Yeung, A.,LeBlanc, E.,Guns, E.,Rennie, P.,Cherkasov, A. (登録日: 2011-04-28, 公開日: 2011-09-21, 最終更新日: 2023-12-20)

主引用文献

Axerio-Cilies, P.,Lack, N.A.,Nayana, M.R.,Chan, K.H.,Yeung, A.,Leblanc, E.,Guns, E.S.,Rennie, P.S.,Cherkasov, A.
Inhibitors of Androgen Receptor Activation Function-2 (Af2) Site Identified Through Virtual Screening.
J.Med.Chem., 54:6197-, 2011

PubMed Abstract: The androgen receptor (AR) is one of the most studied drug targets for the treatment of prostate cancer. However, all current anti-androgens directly interact with the AR at the androgen binding site, which is prone to resistant mutations, calling for new strategies of the AR inhibition. The current study represents the first attempt to use virtual screening to identify inhibitors of activation function-2 (AF2) of the human AR. By combining large-scale docking with experimental approaches, we were able to identify several small molecules that interact with the AF2 and effectively prevent the transcriptional activation of the AR. The crystallographic structure of one of these inhibitors in complex with the AR provides critical insight into the corresponding protein-ligand interactions and suitable for future hit optimization. Taken together, our results provide a promising ground for development of novel anti-androgens that can help to address the problem of drug resistance in prostate cancer.

PubMed: 21846139
DOI: 10.1021/JM200532B

実験手法

X-RAY DIFFRACTION (2.2 Å)