1YIM

Human estrogen receptor alpha ligand-binding domain in complex with compound 4

1YIM の概要

• エントリーDOI: 10.2210/pdb1yim/pdb
• 関連するPDBエントリー: 1YIN
• 分子名称: Estrogen receptor, (2R,3R,4S)-3-(4-HYDROXYPHENYL)-4-METHYL-2-[4-(2-PYRROLIDIN-1-YLETHOXY)PHENYL]CHROMAN-6-OL (3 entities in total)
• 機能のキーワード: nuclear receptor, transcription factor, er-alpha, antagonist, hormone-growth factor receptor complex, hormone/growth factor receptor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28761.87

構造登録者

Fitzgerald, P.M.,Sharma, N. (登録日: 2005-01-12, 公開日: 2005-07-26, 最終更新日: 2024-02-14)

主引用文献

Tan, Q.,Blizzard, T.A.,Morgan, J.D.,Birzin, E.T.,Chan, W.,Yang, Y.T.,Pai, L.Y.,Hayes, E.C.,DaSilva, C.A.,Warrier, S.,Yudkovitz, J.,Wilkinson, H.A.,Sharma, N.,Fitzgerald, P.M.,Li, S.,Colwell, L.,Fisher, J.E.,Adamski, S.,Reszka, A.A.,Kimmel, D.,DiNinno, F.,Rohrer, S.P.,Freedman, L.P.,Schaeffer, J.M.,Hammond, M.L.
Estrogen receptor ligands. Part 10: Chromanes: old scaffolds for new SERAMs.
Bioorg.Med.Chem.Lett., 15:1675-1681, 2005

PubMed Abstract: The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm, and lowered serum cholesterol levels in ovx'd adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs).

PubMed: 15745820
DOI: 10.1016/j.bmcl.2005.01.046

実験手法

X-RAY DIFFRACTION (1.9 Å)