Discovery of a new binding mode for a series of liver X receptor agonists

David J Kopecky; Xian Yun Jiao; Ben Fisher; Sharon McKendry; Marc Labelle; Derek E Piper; Peter Coward; Andrew K Shiau; Patrick Escaron; Jean Danao; Anne Chai; Juan Jaen; Frank Kayser

doi:10.1016/j.bmcl.2012.02.028

Discovery of a new binding mode for a series of liver X receptor agonists

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2407-10. doi: 10.1016/j.bmcl.2012.02.028. Epub 2012 Feb 20.

Authors

David J Kopecky¹, Xian Yun Jiao, Ben Fisher, Sharon McKendry, Marc Labelle, Derek E Piper, Peter Coward, Andrew K Shiau, Patrick Escaron, Jean Danao, Anne Chai, Juan Jaen, Frank Kayser

Affiliation

¹ Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Blvd., South San Francisco, CA 94080, USA. dkopecky@amgen.com

PMID: 22406115
DOI: 10.1016/j.bmcl.2012.02.028

Abstract

Structural modification of a series of dual LXRα/β agonists led to the identification of a new class of LXRβ partial agonists. An X-ray co-crystal structure shows that a representative member of this series, pyrrole 5, binds to LXRβ with a reversed orientation compared to 1.

MeSH terms

Binding Sites
Caco-2 Cells
Crystallography, X-Ray
Genes, Reporter
HEK293 Cells
Humans
Liver X Receptors
Orphan Nuclear Receptors / agonists*
Orphan Nuclear Receptors / chemistry
Protein Binding
Protein Isoforms / agonists*
Protein Isoforms / chemistry
Pyrroles / chemical synthesis*
Pyrroles / pharmacology
Structure-Activity Relationship
Transfection

Substances

Liver X Receptors
NR1H3 protein, human
Orphan Nuclear Receptors
Protein Isoforms
Pyrroles