| CAS |
No.405911-17-3 |
| 英文名称 |
GW3965 Hydrochloride |
| 别名 |
GW3965HCl |
| 分子式 |
C33H31ClF3NO3·HCl |
| 分子量 |
618.51 |
| 溶解性 |
Soluble in DMSO ≥20mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD08276920 |
| SMILES |
ClC1=C(C(F)(F)F)C=CC=C1CN(CC(C2=CC=CC=C2)C3=CC=CC=C3)CCCOC4=CC(CC(O)=O)=CC=C4.[H]Cl |
| InChIKey |
NMPUWJFHNOUNQU-UHFFFAOYSA-N |
| InChI |
InChI=1S/C33H31ClF3NO3.ClH/c34-32-27(15-8-17-30(32)33(35,36)37)22-38(18-9-19-41-28-16-7-10-24(20-28)21-31(39)40)23-29(25-11-3-1-4-12-25)26-13-5-2-6-14-26;/h1-8,10-17,20,29H,9,18-19,21-23H2,(H,39,40);1H |
| PubChem CID |
16078973 |
| 靶点 |
LXR |
| 通路 |
Metabolic Enzyme&Protease |
| 背景说明 |
GW3965 HCl是一种有效的,选择性LXR激动剂。 |
| 生物活性 |
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[1][2][3]. |
| IC50 |
EC50: 190 nM (hLXRα)， 30 nM (hLXRβ)[4] |
| In Vitro |
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[2]. 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[3]. |
| In Vivo |
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[1]. 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[2]. GW3965 hydrochloride (2 mg/kg， i.v.) increases bleeding time and modulated platelet thrombus formation in vivo[3]. |
| 细胞实验 |
Cells are seeded in 96 wells and are treated after 24 hours with different drugs indicated in each experiment in medium containing 1% FBS or lipoprotein deficient serum. Relative proliferation is determined using Cell Proliferation Assay Kit. Cells are incubated 1.5 hrs after adding tetrazolium salt WST-1 [2-(4-iodophenyl)-3- (4-nitrophenyl)-5-(2， 4-disulfo-phenyl)-2H-tetrazolium， monosodium salt] at 5% CO2， 37oC and the absorbance of the treated and untreated cells are measured using a microplate reader at 420 to 480 nm. Cells seeded in 12 well plates are counted using a hemocytometer， and dead cells are assessed using trypan blue exclusion assays.[2] |
| 动物实验 |
Diabetes is induced in two-month-old male rats by a single i.p. injection of freshly prepared STZ (65 mg/kg) in 0.09 M citrate buffer， pH 4.8. Control animals are injected with 0.09 mol/L citrate buffer at pH 4.8. Hyperglycemia is confirmed 48 h after streptozotocin injection by measuring tail vein blood glucose levels using a glucometer OneTouch Ultra2. Only animals with mean plasma glucose levels over 300 mg/mL are classified as diabetic. Glycemia is also assessed before treatment with Ro5-4864 or GW3965 hydrochloride and before death. Two months after STZ injection， diabetic animals are treated once a week with Ro5-4864 (3 mg/kg) or GW3965 hydrochloride (50 mg/kg). Thus， they receive four subcutaneous injections in a month. Control diabetic rats receive 200 μL of vehicle (sesame oil). Four-month-old non-diabetic male rats are injected， following the same experimental schedule， with Ro5-4864， GW3965 hydrochloride or vehicle. Rats are killed 24 h after the last treatment.[1] |
| 数据来源文献 |
[1]. Mitro， Nico.， et al. LXR and TSPO as new therapeutic targets to increase the levels of neuroactive steroids in the central nervous system of diabetic animals. Neurochemistry International (2012)， 60(6)， 616-621.
[2]. Guo， Deliang.， et al. An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR-Dependent Pathway. Cancer Discovery (2011)， 1(5)， 442-456.
[3]. Spyridon， Michael.， et al. LXR as a novel antithrombotic target. Blood (2011)， 117(21)， 5751-5761.
[4]. Collins JL， et al. Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J Med Chem. 2002 May 9;45(10):1963-6. |
| 规格 |
1mg 5mg 10mM*1mL in DMSO 10mg 25mg 50mg |
| 单位 |
支 |
中文
英语
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