Structural basis of estrogen receptor partial agonist and SERM agonist activities

COMP 5

Kendall W. Nettles, knettles@scripps.edu1, Hai-Bing Zhou2, John A. Katzenellenbogen, jkatzene@uiuc.edu2, and Geoffrey L. Greene3. (1) Department of Biochemistry, The Scripps Research Institute, 5353 Parkside Dr. RF-1, Jupiter, FL 33458, (2) Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, (3) The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637
Nuclear receptor therapeutics act by modulating the recruitment of transcriptional coregulator proteins to the ligand-binding domain. X-ray crystallography has proven successful at providing structural details of ligand-receptor complexes. However, the mechanisms of communication between ligand and cofactor binding sites have remained elusive, limiting the utility of structural data to guide medicinal chemistry efforts. The structural features that define partial agonist activity for the estrogen receptor will be explained, with a focus on predictive chemistry. The structural features that define Selective Estrogen Receptor Modulator (SERM) agonist activity in the uterus will also be addressed.
 

Structure-Based Design & Development of Estrogen Receptor Modulators
9:00 AM-12:35 PM, Sunday, 10 September 2006 Moscone Center -- Room 224/226, Oral

Division of Computers in Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006