6SUO

ERa_L536S (L536S/C381S/C471S,C530S) in complex with a tricyclic indole (compound 6)

6SUO の概要

• エントリーDOI: 10.2210/pdb6suo/pdb
• 分子名称: Estrogen receptor, (~{E})-3-[3,5-bis(fluoranyl)-4-[(1~{R},3~{R})-2-(2-fluoranyl-2-methyl-propyl)-1,3-dimethyl-4,9-dihydro-3~{H}-pyrido[3,4-b]indol-1-yl]phenyl]prop-2-enoic acid (3 entities in total)
• 機能のキーワード: oestrogen receptor, oestrogen binding domain, gene regulation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58224.04

構造登録者

Breed, J. (登録日: 2019-09-16, 公開日: 2019-10-30, 最終更新日: 2024-05-15)

主引用文献

Scott, J.S.,Breed, J.,Carbajo, R.J.,Davey, P.R.,Greenwood, R.,Huynh, H.K.,Klinowska, T.,Morrow, C.J.,Moss, T.A.,Polanski, R.,Nissink, J.W.M.,Varnes, J.,Yang, B.
Building Bridges in a Series of Estrogen Receptor Degraders: An Application of Metathesis in Medicinal Chemistry.
Acs Med.Chem.Lett., 10:1492-1497, 2019

PubMed Abstract: Herein we report the use of metathesis to construct a novel tetracyclic core in a series of estrogen receptor degraders. This improved the chemical stability, as assessed using an NMR-MS based assay, and gave a molecule with excellent physicochemical properties and pharmacokinetics in rat. X-ray crystallography established minimal perturbation of the bridged compounds relative to the unbridged analogues in the receptor binding pocket. Unfortunately, despite retaining excellent binding to ERα, this adversely affected the ability of the compounds to degrade the receptor.

PubMed: 31620239
DOI: 10.1021/acsmedchemlett.9b00370

実験手法

X-RAY DIFFRACTION (1.74 Å)