GW3965 is a potent and selective agonist of liver X receptor (LXR) with EC50 values of 190 nM for hLXRα and 30 nM for hLXRβ [1] [2] [3].

GW3965 effectively induces death in GBM cells in vitro, particularly in those expressing EGFRvIII. It enhances the expression of the cholesterol transporter gene ABCA1 and the E3 ubiquitin ligase IDOL, while decreasing LDLR levels. Furthermore, LXR ligands, including GW3965, can suppress both platelet aggregation and calcium mobilization induced by collagen or CRP. Although at lower concentrations (1 or 5 μM), GW3965 slightly inhibits fibrinogen binding and P-selectin exposure in platelets activated by 1 μg/mL CRP, higher doses of GW3965 (10 μM) or T0901317 (40 μM) significantly diminish fibrinogen and P-selectin levels on the platelet surface.

GW3965 elevates neuroactive steroids in the spinal cord, cerebellum, and cerebral cortex of STZ-rats, not affecting the CNS in non-pathological subjects. It also enhances dihydroprogesterone levels and myelin basic protein expression in the spinal cord of diabetic rats [1]. At a dose of 40 mg/kg orally, GW3965 significantly upregulates ABCA1 expression and downregulates LDLR expression, which correlates with a 59% reduction in tumor growth and a substantial increase in GBM cell apoptosis by 25 times in vivo [2]. Additionally, administered intravenously at 2 mg/kg, GW3965 prolongs bleeding time and modulates platelet thrombus formation in vivo [3].