5T97

ESTROGEN RECEPTOR ALPHA LIGAND BINDING DOMAIN IN COMPLEX WITH (2E)-3-(4-{(1R)-6-hydroxy-1-methyl-2-[4-(propan-2 -yl)phenyl]-1,2,3,4- tetrahydroisoquinolin-1-yl}phenyl)prop-2-enoic acid

5T97 の概要

• エントリーDOI: 10.2210/pdb5t97/pdb
• 関連するPDBエントリー: 5T92
• 分子名称: Estrogen receptor, (2E)-3-(4-{(1R)-6-hydroxy-1-methyl-2-[4-(propan-2-yl)phenyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}phenyl)prop-2-enoic acid (3 entities in total)
• 機能のキーワード: nuclear receptor, protein-ligand complex, hormone 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: 2
• 化学式量合計: 58650.82

構造登録者

Kirby, C.A.,Baird, J. (登録日: 2016-09-09, 公開日: 2017-03-29, 最終更新日: 2024-03-06)

主引用文献

Burks, H.E.,Abrams, T.,Kirby, C.A.,Baird, J.,Fekete, A.,Hamann, L.G.,Kim, S.,Lombardo, F.,Loo, A.,Lubicka, D.,Macchi, K.,McDonnell, D.P.,Mishina, Y.,Norris, J.D.,Nunez, J.,Saran, C.,Sun, Y.,Thomsen, N.M.,Wang, C.,Wang, J.,Peukert, S.
Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ER alpha + Breast Cancer.
J. Med. Chem., 60:2790-2818, 2017

PubMed Abstract: Tetrahydroisoquinoline 40 has been identified as a potent ERα antagonist and selective estrogen receptor degrader (SERD), exhibiting good oral bioavailability, antitumor efficacy, and SERD activity in vivo. We outline the discovery and chemical optimization of the THIQ scaffold leading to THIQ 40 and showcase the racemization of the scaffold, pharmacokinetic studies in preclinical species, and the in vivo efficacy of THIQ 40 in a MCF-7 human breast cancer xenograft model.

PubMed: 28296398
DOI: 10.1021/acs.jmedchem.6b01468

実験手法

X-RAY DIFFRACTION (3 Å)