GW3965 is a potent, selective agonist of liver X receptor (LXR) with EC 50 s of 190 nM and 30 nM for hLXRα and hLXRβ, respectively [1] [2] [3].

GW3965 promotes GBM cell death in vitro with enhanced efficacy in EGFRvIII-expressing tumor cells. GW3965 up-regulates expression of the cholesterol transporter gene ABCA1 and the E3 ubiquitin ligase IDOL and reduces LDLR levels [2]. LXR ligands inhibits platelet aggregation and calcium mobilization stimulated by collagen or CRP. GW3965 (1 or 5 μM) shows a minor inhibitory effect on fibrinogen binding and P-selectin exposure, when platelets are stimulated with 1 μg/mL CRP. But using higher concentrations of GW3965 (10 μM) or T0901317 (40 μM), the levels of fibrinogen and P-selectin on the platelet surface are reduced [3].

GW3965 induces an increase of neuroactive steroids in the spinal cord, the cerebellum and the cerebral cortex of STZ-rats, but not in the CNS of non-pathological animals. GW3965 treatment induces an increase of dihydroprogesterone in the spinal cord of diabetic animals in association with an increase of myelin basic protein expression [1]. GW3965 (40 mg/kg, p.o.) strongly induces ABCA1 expression and reduces LDLR expression, and this is accompanied by 59% inhibition of tumor growth, and a 25-fold increase in GBM cell apoptosis in vivo [2]. GW3965 (2 mg/kg, i.v.) increases bleeding time and regulated platelet thrombus formation in vivo [3].