Structure of the farnesoid X receptor ligand binding domain and methods of use therefor
US7647217B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Nov 14, 2003 |
| Grant date | Jan 12, 2010 |
| Priority date | — |
| Expiry date | Aug 6, 2024 |
Classification
- Technology area (CPC G)Physics
- CPC primaryG16B15/00
- WIPO fieldMeasurement
- WIPO sectorInstruments
Abstract
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 three-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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.