X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain

被引：91

作者：

Biggadike, Keith ^{[1
]}

Bledsoe, Randy K. ^{[4
]}

Hassell, Anne M. ^{[4
]}

Kirk, Barrie E. ^{[1
]}

McLay, Iain M. ^{[2
]}

Shewchuk, Lisa M. ^{[4
]}

Stewart, Eugene L. ^{[3
]}

机构：

[1] GlaxoSmithKline Med Res Ctr, Dept Med Chem, Stevenage SG1 2NY, Herts, England

[2] GlaxoSmithKline Med Res Ctr, Dept Computat Chem, Stevenage SG1 2NY, Herts, England

[3] GlaxoSmithKline, Dept Computat Chem, Res Triangle Pk, NC 27709 USA

[4] GlaxoSmithKline, Dept Biol Struct, Res Triangle Pk, NC 27709 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 12期

关键词：

D O I：

10.1021/jm800279t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

An X-ray crystal structure is reported for the novel enhanced-affinity glucocorticoid agonist fluticasone furoate (FF) in the ligand binding domain of the glucocorticoid receptor. Comparison of this structure with those of dexamethasone and fluticasone propionate shows the 17 alpha furoate ester to occupy more fully the lipophilic 17 alpha pocket on the receptor, which may account for the enhanced glucocorticoid receptor binding of FF.

引用

页码：3349 / 3352

页数：4

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