GW3965 hydrochloride is a potent and selective liver X receptor (LXR) agonist with EC50s of 190 nM and 30 nM for hLXRα and hLXRβ, respectively.
IC50&Target
EC50: 190 nM (hLXRα), 30 nM (hLXRβ)
体外研究
GW3965 hydrochloride promotes GBM cell death in vitro with enhanced efficacy in EGFRvIII-expressing tumor cells. GW3965 hydrochloride up-regulates expression of the cholesterol transporter gene ABCA1 and the E3 ubiquitin ligase IDOL and reduces LDLR levels. LXR ligands inhibits platelet aggregation and calcium mobilization stimulated by collagen or CRP. GW3965 hydrochloride (1 or 5 μM) displays 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 hydrochloride (10 μM) or T0901317 (40 μM), the levels of fibrinogen and P-selectin on the platelet surface are reduced.
体内研究
GW3965 hydrochloride 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 hydrochloride treatment induces an increase of dihydroprogesterone in the spinal cord of diabetic animals in association with an increase of myelin basic protein expression. GW3965 hydrochloride (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. GW3965 hydrochloride (2 mg/kg, i.v.) increases bleeding time and modulated platelet thrombus formation in vivo.
分子式
C33H32Cl2F3NO3
分子量
618.51
CAS号
405911-17-3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 100 mg/mL (161.68 mM; Need ultrasonic)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)