3V49

Structure of ar lbd with activator peptide and sarm inhibitor 1

3V49 の概要

• エントリーDOI: 10.2210/pdb3v49/pdb
• 関連するPDBエントリー: 2AMA 2Z4J 3V4A
• 分子名称: Androgen receptor, Androgen receptor, activator peptide, 4-[(4R)-4-(4-hydroxyphenyl)-3,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile, ... (5 entities in total)
• 機能のキーワード: diarylhydantoin, synthesis, sarm, antiandrogen, ligand binding domain, testosterone, dihydrotestosterone, transcription, sarm (selective androgen receptor modulator)
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : P10275 P10275
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32748.99

構造登録者

Nique, F.,Hebbe, S.,Peixoto, C.,Annoot, D.,Lefrancois, J.-M.,Duval, E.,Michoux, L.,Triballeau, N.,Lemoullec, J.-M.,Mollat, P.,Thauvin, M.,Prange, T.,Minet, D.,Clement-Lacroix, P.,Robin-Jagerschmidt, C.,Fleury, D.,Guedin, D.,Deprez, P. (登録日: 2011-12-14, 公開日: 2012-09-05, 最終更新日: 2023-09-13)

主引用文献

Nique, F.,Hebbe, S.,Peixoto, C.,Annoot, D.,Lefrancois, J.-M.,Duval, E.,Michoux, L.,Triballeau, N.,Lemoullec, J.M.,Mollat, P.,Thauvin, M.,Prange, T.,Minet, D.,Clement-Lacroix, P.,Robin-Jagerschmidt, C.,Fleury, D.,Guedin, D.,Deprez, P.
Discovery of diarylhydantoins as new selective androgen receptor modulators.
J.Med.Chem., 55:8225-8235, 2012

PubMed Abstract: A novel selective androgen receptor modulator scaffold has been discovered through structural modifications of hydantoin antiandrogens. Several 4-(4-hydroxyphenyl)-N-arylhydantoins displayed partial agonism with nanomolar in vitro potency in transactivation experiments using androgen receptor (AR) transfected cells. In a standard castrated male rat model, several compounds showed good anabolic activity on levator ani muscle, dissociated from the androgenic activity on ventral prostate, after oral dosing at 30 mg/kg. (+)-4-[3,4-Dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile ((+)-11b) displayed anabolic potency with a strong dissociation between levator ani muscle and ventral prostate (A(50) = 0.5 mg/kg vs 70 mg/kg). The binding modes of two compounds, including (+)-11b, within the AR ligand-binding domain have been studied by cocrystallization experiments using a coactivator-like peptide. Both compounds bound to the same site, and the overall structures of the AR were very similar.

PubMed: 22897611
DOI: 10.1021/jm300249m

実験手法

X-RAY DIFFRACTION (1.7 Å)