Michael R. Downes,Mark A. Verdicia,Joseph P. Noel,Ronald M. Evans,Lindsey J. Bowman,Marianne Bowman
申请号：
US12686347
公开号：
US08212006B2
申请日:
2010.01.12
申请国别(地区):
US
年份:
2012
代理人:
摘要：
The present invention provides compositions comprising the ligand binding domain (LBD) of a farnesoid X receptor (FXR) in crystalline form. In alternative embodiments, the LBD of FXR is complexed with a ligand therefor. There are provided high resolution structures of FXR complexed with a novel high affinity agonist fexaramine. The discovered structure of a FXR LBD provides the first three-dimensional view of the structural basis for FXR ligand binding. The present invention further provides a computer for producing a time-dimensional representation of FXR or a complex thereof, and a computer for determining at least a portion of the structure coordinates of FXR or a complex thereof. The present invention further provides methods of using this structural information to predict molecules capable of binding to FXR to identify compounds with agonist, antagonist or partial agonist activity for FXR and to determine whether a test compound is capable of binding to the LBD of FXR. The present invention further provides compositions comprising compounds identified by such invention methods.
