Abstract
A potent, selective, orally active LXR agonist was identified from focused libraries of tertiary amines. GW3965 (12) recruits the steroid receptor coactivator 1 to human LXRα in a cell-free ligand-sensing assay with an EC50 of 125 nM and profiles as a full agonist on hLXRα and hLXRβ in cell-based reporter gene assays with EC50's of 190 and 30 nM, respectively. After oral dosing at 10 mg/kg to C57BL/6 mice, 12 increased expression of the reverse cholesterol transporter ABCA1 in the small intestine and peripheral macrophages and increased the plasma concentrations of HDL cholesterol by 30%. 12 will be a valuable chemical tool to investigate the role of LXR in the regulation of reverse cholesterol transport and lipid metabolism.
Original language | English (US) |
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Pages (from-to) | 1963-1966 |
Number of pages | 4 |
Journal | Journal of Medicinal Chemistry |
Volume | 45 |
Issue number | 10 |
DOIs | |
State | Published - May 9 2002 |
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery