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GW3965 HCl Catalog No.GC17696

LXR agonist, selective and orally active

Size Price Stock Qty
10mM (in 1mL DMSO)
$67.00
In stock
5mg
$50.00
In stock
10mg
$80.00
In stock
50mg
$288.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

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Protocol

Cell experiment:

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.

Animal experiment:

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.

References:

[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.

Chemical Properties

Cas No. 405911-17-3 SDF
Chemical Name 2-[3-[3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]propoxy]phenyl]acetic acid;hydrochloride
Canonical SMILES C1=CC=C(C=C1)C(CN(CCCOC2=CC=CC(=C2)CC(=O)O)CC3=C(C(=CC=C3)C(F)(F)F)Cl)C4=CC=CC=C4.Cl
Formula C33H31ClF3NO3.HCl M.Wt 618.51
Solubility ≥30.55mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
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Background

GW3965 HCl is a selective, orally active non-steroidal agonist for the liver X receptor (LXR) [1].
Nuclear receptors LXRα  and LXRβ have an important role in control of cholesterol and fatty acid metabolism in multiple cell types. Activation of these receptors promotes bile acid synthesis in liver, inhibits intestinal cholesterol absorption and stimulates cholesterol efflux in macrophages, which will then reduce atherosclerotic risk [2].
In a cell-free ligand-sensing assay, GW3965 recruits the steroid receptor coactivator 1 to human LXRR with an EC50 of 125 nM. In cell-based reporter gene assays, GW3965 plays as a full agonist on hLXRα and hLXRβ with EC50 of 190 and 30 nM, respectively [1].
Treatment C57BL/6 mice with 10 mg/kg GW3965 HCl orally, GW3965 HCl increased the plasma concentrations of HDL cholesterol by 30% and enhanced the expression of the reverse cholesterol transporter ABCA1 in the small intestine and peripheral macrophages [1]. In male Sprague–Dawley rats, GW3965 decreased Ang II-mediated vasopressor responses and reduced ATR gene expression, which suggested GW3965 can affect vascular reactivity [3].
References:
[1]. Collins JL, Fivush AM, Watson MA, et al. Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J Med Chem, 2002, 45(10): 1963-1966.
[2]. Joseph SB, McKilligin E, Pei L, et al. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci U S A, 2002, 99(11): 7604-7609.
[3]. Leik CE, Carson NL, Hennan JK, et al. GW3965, a synthetic liver X receptor (LXR) agonist, reduces angiotensin II-mediated pressor responses in Sprague-Dawley rats. Br J Pharmacol, 2007, 151(4): 450-456.