Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines
JL Collins, AM Fivush, MA Watson… - Journal of medicinal …, 2002 - ACS Publications
JL Collins, AM Fivush, MA Watson, CM Galardi, MC Lewis, LB Moore, DJ Parks, JG Wilson…
Journal of medicinal chemistry, 2002•ACS PublicationsA 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 …
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 …
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.
ACS Publications