X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain.
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.
kb0903@gsk.com
Keith
K
Biggadike
Randy K
RK
Bledsoe
Anne M
AM
Hassell
Barrie E
BE
Kirk
Iain M
IM
McLay
Lisa M
LM
Shewchuk
Eugene L
EL
Stewart
D000730:Androstadienes / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D051958:Nuclear Receptor Coactivator 2 / Q000737:chemistry; D011487:Protein Conformation; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000737:chemistry*
D000730:Androstadienes; D051958:Nuclear Receptor Coactivator 2; D011965:Receptors, Glucocorticoid; C523187:fluticasone furoate