Discovery of tertiary sulfonamides as potent liver X receptor antagonists.
Article Details
- CitationCopy to clipboard
Zuercher WJ, Buckholz RG, Campobasso N, Collins JL, Galardi CM, Gampe RT, Hyatt SM, Merrihew SL, Moore JT, Oplinger JA, Reid PR, Spearing PK, Stanley TB, Stewart EL, Willson TM
Discovery of tertiary sulfonamides as potent liver X receptor antagonists.
J Med Chem. 2010 Apr 22;53(8):3412-6. doi: 10.1021/jm901797p.
- PubMed ID
- 20345102 [ View in PubMed]
- Abstract
Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) TO-901317 Oxysterols receptor LXR-alpha EC 50 (nM) 63.1 N/A N/A Details