GW3965 HCl

GW3965 recruits the steroid receptor coactivator 1 to human LXRα with EC50 of 125 nM in a cell-free ligand-sensing assay. ^[1]

GW3965 shows a potent antagonistic activity against hLXRα and hLXRβ in cell-based assays with EC50 of 190 nM and 30 nM, respectively. Besides, GW3965 also sows excellent selectivity over other nuclear receptors. ^[1]

In human islets, GW3965 (1 μM) reduces expression of selected pro-inflammatory cytokines including IL-8, monocyte chemotactic protein-1 and tissue factor. ^[4]

In mice, GW3965 at a dose of 10 mg/kg upregulates ABCA1 expression 8-fold and raises circulating levels of HDL by 30% with C_max of 12.7 μg/mL and t_1/2 of 2 hours. ^[1]

GW3965 (10mg/kg) induces expression of ABCA1 and ABCG1 and shows potent antiatherogenic activity in both LDLR−/− and apoE−/− mice. ^[2]

In male sprague-dawley rats, GW3965 reduces Ang II-mediated increases in blood pressure and decreases vascular Ang II receptor gene expression. ^[3]

In Glioblastoma mouse model, GW3965 results in inducible degrader of LDLR-mediated LDLR degradation, increased expression of the ABCA1 cholesterol efflux transporter, and thus potently promotes tumor cell death. ^[5]

• Animal Models

  C57BL/6 mice

• Dosages

  ≤10 mg/kg

• Administration

  Administered via p.o.