GW 3965 HYDROCHLORIDE

GW 3965 HYDROCHLORIDE - Names and Identifiers

Name	2-(3-(3-((2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid hydrochloride
Synonyms	GW3965 HCl GW3965 HCl Salt GW3965 hydrochloride GW 3965 HYDROCHLORIDE 3-[3-[n-(2-chloro-3-trifluoroMethylbenzyl)-(2,2-di… 3-[3-[n-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)amino]propyloxy]phenylacetic acid hydrochloride 2-[3-[3-[[2-Chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]propoxy]phenyl]acetic acid hydrochloride 2-(3-(3-((2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid hydrochloride 3-[3-[[[2-Chloro-3-(trifluoromethyl)phenyl]methyl](2,2-diphenylethyl)amino]propoxy]benzeneacetic acid hydrochloride Benzeneacetic acid, 3-[3-[[[2-chloro-3-(trifluoromethyl)phenyl]methyl](2,2-diphenylethyl)amino]propoxy]-, hydrochloride
CAS	405911-17-3
InChIKey	NMPUWJFHNOUNQU-UHFFFAOYSA-N

GW 3965 HYDROCHLORIDE - Physico-chemical Properties

Molecular Formula	C33H31ClF3NO3.HCl
Solubility	DMSO : 70 mg/mL (ultrasonic) Mother Liquor Preservation: Sub-packing and freezing to avoid repeated freezing and thawing;-20 ℃,1 month;-80 ℃,6 months (after dilution, the solution temperature is low and storage may precipitate, as far as possible) Cell experiment: Dissolve with DMSO first: dilute with culture medium then, and the dilution process is recommended to be carried out in stages to avoid too fast concentration change leading to compound precipitation. If the compound is precipitated during the dilution process, it can be redissolved by ultrasound. During dilution, ensure that the final concentration of DMSO in the working fluid should be below 0.1% as far as possible, and the maximum should not exceed 0.5%, and set up a DMSO control group with corresponding concentration. Animal experiment: Dissolve with DMSO first: dilute with water or normal saline, etc. The dilution process is recommended to be carried out in sections to avoid excessive concentration changes leading to co
Appearance	powder
Color	white
Storage Condition	-20°C
MDL	MFCD08276920
Use	GW-3965 is a liver X receptor agonist. GW3965 represses the production of pro-inflammatory cytokines by murine mast cells. GW3965 improves recovery from mild repetitive traumatic brain injury in mice partly through apolipoprotein E. GW3965 reduces tissue factor production and inflammatory responses in human islets in vitro. GW3965 dose-dependently regulates lps-mediated liver injury and modulates posttranscriptional TNF-alpha production and p38 mitogen-activated protein kinase activation in liver macrophages.
Target	hLXRα;hLXRβ;LXRα/SRC1 LiSA
In vitro study	GW3965 aggregates steroid receptor coactivator 1 to lxrα with an EC50 of 125 nM in the cell-free Ligand Detection Assay. GW3965 exhibited potent antagonistic activity against hLXR α and hLXR β with EC50 of 190 nM and 30 nM, respectively, in the cell assay. In addition, GW3965 also showed excellent selectivity for other nuclear receptors. In human islets, GW3965 (1 μm) reduced the expression of selected pro-inflammatory cytokines, including IL-8, monocyte chemoattractant protein -1 and tissue factor.
In vivo study	In mice, GW3965 at a dose of 10 mg/kg up-regulates ABCA1 expression by 8-fold and increases circulating levels by 30% with a C max of 12.7 μg/mL ,t 1/2 is 2 hours. In LDLR −/− and apoE −/− mice, GW3965 (10mg/kg) induced ABCA1 and ABCG1 expression and exhibited potent anti-atherosclerotic activity. GW3965 reduced Ang II-mediated increase in blood pressure and reduced vascular Ang II receptor gene expression in male sprague-dawley rats. In a mouse model of malignant glioma, GW3965 leads to degradation of LDLR and increases the expression of ABCA1 cholesterol efflux transporter, thereby effectively promoting tumor cell death.

GW 3965 HYDROCHLORIDE - Risk and Safety

Hazard Symbols	Xn - Harmful
Risk Codes	R22 - Harmful if swallowed R41 - Risk of serious damage to eyes
Safety Description	S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S39 - Wear eye / face protection.
WGK Germany	3

GW 3965 HYDROCHLORIDE - Reference

Reference

1: Wang R, Li R, Wen Q, Peng K, Tan X, Chen Z. [Expression of LXR-β in human gastric cancer tissue and the effect of GW3965 on the proliferation of gastric cancer cell line SGC-7901]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016 Feb 28;41(2):127-33. doi: 10.11817/j.issn.1672-7347.2016.02.003. Chinese. PubMed PMID: 26932209.
2: Nunomura S, Okayama Y, Matsumoto K, Hashimoto N, Endo-Umeda K, Terui T, Makishima M, Ra C. Activation of LXRs using the synthetic agonist GW3965 represses the production of pro-inflammatory cytokines by murine mast cells. Allergol Int. 2015 Sep;64 Suppl:S11-7. doi: 10.1016/j.alit.2015.03.001. Epub 2015 Mar 31. PubMed PMID: 26344074.
3: Archer A, Stolarczyk E, Doria ML, Helguero L, Domingues R, Howard JK, Mode A, Korach-André M, Gustafsson JÅ. LXR activation by GW3965 alters fat tissue distribution and adipose tissue inflammation in ob/ob female mice. J Lipid Res. 2013 May;54(5):1300-11. doi: 10.1194/jlr.M033977. Epub 2013 Feb 27. PubMed PMID: 23446231; PubMed Central PMCID: PMC3622325.
4: Namjoshi DR, Martin G, Donkin J, Wilkinson A, Stukas S, Fan J, Carr M, Tabarestani S, Wuerth K, Hancock RE, Wellington CL. The liver X receptor agonist GW3965 improves recovery from mild repetitive traumatic brain injury in mice partly through apolipoprotein E. PLoS One. 2013;8(1):e53529. doi: 10.1371/journal.pone.0053529. Epub 2013 Jan 17. PubMed PMID: 23349715; PubMed Central PMCID: PMC3547922.
5: Cui X, Chopp M, Zacharek A, Cui Y, Roberts C, Chen J. The neurorestorative benefit of

GW 3965 HYDROCHLORIDE - Preparation solution concentration reference

	1mg	5mg	10mg
1 mM	1.617 ml	8.084 ml	16.168 ml
5 mM	0.323 ml	1.617 ml	3.234 ml
10 mM	0.162 ml	0.808 ml	1.617 ml
5 mM	0.032 ml	0.162 ml	0.323 ml

Last Update：2024-01-02 23:10:35

GW 3965 HYDROCHLORIDE - 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.

Last Update：2023-08-16 21:32:38

GW 3965 HYDROCHLORIDE - Introduction

2-(3-(3-((2-chroo-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid hydrochloride is a compound, its chemical name is 1-(4-(2-(3-(4-chroophenyl) propoxy)-5-methylpyrimidin-4-yl)phenyl)-3-(4-(phenyl) phenyl)urea hydrochloride. It is a fatty acid receptor activator (fatty acid receptor agonist), which is widely used in biomedical research.

2-(3-(3-((2-choro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid hydrochloride is mainly used to activate the nuclear receptor transcription factor LXR(liver X receptor), thereby regulating cholesterol and lipid metabolism. LXR is a transcription factor that regulates cholesterol synthesis and transport by activating LXR,2-(3-((2-chroo-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid hydrochloride can affect lipid metabolism pathways and has a variety of biological activities such as anti-inflammatory, antioxidant and anti-tumor.

Preparation of 2-(3-(3-((2-choro-3-(trifluoromethyl)benzyl)(2,2-diphenyl ethyl)amino)propoxy)phenyl) the method of acetic acid hydrochloride is generally a synthetic organic synthetic route. First, the precursor compound of GW3965 is synthesized by chemical method, and then 2-(3-((2-chloro-3-(trifluoromethyl)benzyl)(2) is formed by adding HCl acid, 2-diphenyl ethyl)amino)propoxy)phenyl)acetic acid hydrochloride.

2-(3-(3-((2-choro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid hydrochloride has limited safety information. When using it, you should follow the laboratory safety procedures and strictly control the dosage. In addition, 2-(3-(3-((2-choro-3-(trifluoromethyl)benzyl)(2,2-diphenyl ethyl)amino)propoxy)phenyl)acetic acid hydrochloride should be stored in a dry, cool place, avoid light and damp. When used, avoid inhalation, ingestion or contact with skin and eyes. In case of accidental contact, rinse immediately with plenty of water and seek medical help.

Last Update：2024-04-09 21:01:54