发明名称 |
Structure of the farnesoid X receptor ligand binding domain and methods of use therefor |
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. |
申请公布号 |
US8212006(B2) |
申请公布日期 |
2012.07.03 |
申请号 |
US20100686347 |
申请日期 |
2010.01.12 |
申请人 |
DOWNES MICHAEL R.;VERDICIA MARK A.;NOEL JOSEPH P.;EVANS RONALD M.;BOWMAN LINDSEY J.;BOWMAN MARIANNE;THE SALK INSTITUTE FOR BIOLOGICAL STUDIES |
发明人 |
DOWNES MICHAEL R.;VERDICIA MARK A.;NOEL JOSEPH P.;EVANS RONALD M.;BOWMAN LINDSEY J.;BOWMAN MARIANNE |
分类号 |
C07K1/00;A01N61/00;C07K14/705;G06F19/00;G06F19/16;G06G7/58 |
主分类号 |
C07K1/00 |
代理机构 |
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