| Literature DB >> 11985463 |
Jon L Collins, Adam M Fivush, Michael A Watson, Cristin M Galardi, Michael C Lewis, Linda B Moore, Derek J Parks, Joan G Wilson, Tim K Tippin, Jane G Binz, Kelli D Plunket, Daniel G Morgan, Elizabeth J Beaudet, Karl D Whitney, Steven A Kliewer, Timothy M Willson.
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 LXRalpha in a cell-free ligand-sensing assay with an EC(50) of 125 nM and profiles as a full agonist on hLXRalpha and hLXRbeta in cell-based reporter gene assays with EC(50)'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.Entities:
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Year: 2002 PMID： 11985463 DOI： 10.1021/jm0255116
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446