The first X-ray crystal structure of the glucocorticoid receptor bound to a non-steroidal agonist

Kevin P Madauss; Randy K Bledsoe; Iain Mclay; Eugene L Stewart; Iain J Uings; Gordon Weingarten; Shawn P Williams

doi:10.1016/j.bmcl.2008.10.021

The first X-ray crystal structure of the glucocorticoid receptor bound to a non-steroidal agonist

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6097-9. doi: 10.1016/j.bmcl.2008.10.021. Epub 2008 Oct 8.

Authors

Kevin P Madauss¹, Randy K Bledsoe, Iain Mclay, Eugene L Stewart, Iain J Uings, Gordon Weingarten, Shawn P Williams

Affiliation

¹ Department of Computational and Structural Chemistry, Molecular Discovery Research, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. kevin.p.madauss@gsk.com

PMID: 18952422
DOI: 10.1016/j.bmcl.2008.10.021

Abstract

The amino-pyrazole 2,6-dichloro-N-ethyl benzamide 1 is a selective GR agonist with dexamethasone-like in vitro potency. Its X-ray crystal structure in the GR LBD (Glucocorticoid ligand-binding domain) is described and compared to other reported structures of steroidal GR agonists in the GR LBD (3E7C).

MeSH terms

Benzamides / chemical synthesis*
Benzamides / chemistry
Benzamides / pharmacology*
Crystallography, X-Ray
Dexamethasone / chemistry
Dexamethasone / pharmacology*
Models, Molecular*
Molecular Conformation
Molecular Structure
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Receptors, Glucocorticoid / agonists*
Structure-Activity Relationship

Substances

Benzamides
Pyrazoles
Receptors, Glucocorticoid
amino-pyrazole 2,6-dichloro-N-ethyl benzamide
Dexamethasone