GW3965 HCl

目录号：S2630 Purity: 99.88%

GW3965 HCl是一种有效的，选择性LXR激动剂，作用于hLXRα和hLXRβ，无细胞试验中EC50分别为190和30 nM。

GW3965 HCl Chemical Structure

CAS: 405911-17-3

规格	价格	库存
10mM (1mL in DMSO)	1966.57	现货
5mg	790.51	现货
50mg	4654.57	现货
200mg	7944.3	现货
1g	27764.1	现货
更大包装有超大折扣
400-668-6834 info@selleck.cn

产品质控

批次：纯度： 99.88%

99.88

常与GW3965 HCl一起在实验中被使用的化合物

Carboplatin

在MAS98.12模型中，GW3965和Carboplatin比单独Carboplatin显着减小相对肿瘤体积。

Haugen MH, et al. Mol Oncol. 2023 Jun 21.

Pioglitazone

GW3965和Pioglitazone组合预处理原代小胶质细胞可导致iNOS转录物显着减少。

Skerrett R, et al. J Biol Chem. 2015 Aug 28;290(35):21591-602.

Bexarotene

GW3965HCl和Bexarotene诱导急性髓系白血病(AML)细胞的分化和凋亡。

Serhan N, et al. Cancers (Basel). 2020 Jun 29;12(7):1725.

Gefitinib

GW3965可以增加Gefitinib诱导的HCC827/GR-8-2细胞系细胞凋亡和细胞周期停滞。

Hu Y, et al. Oncotarget. 2017 Feb 28;8(9):15802-15814.

Navitoclax (ABT-263)

在A375异种移植模型中，GW3965和Navitoclax(ABT-263)联合治疗比单独使用任一药物更能明显抑制肿瘤生长。

Nguyen TTT, et al. EMBO Mol Med. 2019 Oct;11(10):e10769.

GW3965 HCl相关产品

相关靶点	LXR-α LXR-β	点击展开
相关产品	T0901317 LXR-623 SR9243 AZ876	点击展开
相关化合物库	代谢化合物库抗癌代谢化合物库谷氨酰胺代谢化合物库糖代谢化合物库脂代谢化合物库	点击展开

细胞实验数据示例

细胞系	实验类型	给药浓度	孵育时间	活性描述	文献信息
HEK293		10 uM	20 hrs	Activation of rat LXRbeta expressed in HEK293 cells co-expressing human RXRalpha at 10 uM after 20 hrs by luciferase reporter gene assay	28006909
HEK293		10 uM	20 hrs	Activation of human LXRalpha expressed in HEK293 cells co-expressing human RXRalpha at 10 uM after 20 hrs by luciferase reporter gene assay	28006909
HepG2	Function assay	500 nM		Inhibition of 2-(3-(3-((2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid-induced srebp1c mRNA expression in human HepG2 cells at 500 nM	18800767
HepG2	Function assay	500 nM		Inhibition of 2-(3-(3-((2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid-induced fas mRNA expression in human HepG2 cells at 500 nM	18800767
RAW264.7	Function assay	1 uM		Reduction of LPS-stimulated iNOS gene expression in mouse RAW264.7 cells expressing LXRalpha at 1 uM by luciferase reporter gene assay	18800767
RAW264.7	Function assay	1 uM		Inhibition of LPS-stimulated nuclear co-repressor release from iNOS promoter in mouse RAW264.7 cells at 1 uM by RT-PCR	18800767
HeLa	Function assay	1 uM		Induction of LXRbeta SUMOylation by SUMO2 in human HeLa cells at 1 uM by Western blot analysis	18800767
HeLa	Function assay	1 uM		Induction of LXRbeta SUMOylation by SUMO3 in human HeLa cells at 1 uM by Western blot analysis	18800767
HeLa	Function assay	1 uM		Induction of LXRalpha SUMOylation by SUMO3 in human HeLa cells at 1 uM by Western blot analysis	18800767
THP1	Antiinflammatory assay		6 hrs	Antiinflammatory activity against human THP1 cells assessed as inhibition of LPS-stimulated IL6 production after 6 hrs by ELISA, IC50 = 0.02 μM.	18800767
COS7	Function assay		16 hrs	Agonist activity at human LXRbeta receptor transfected in COS7 cells after 16 hrs by reporter transactivation assay, EC50 = 0.015 μM.	17587573
THP1	Function assay		18 hrs	Induction of cholesterol efflux in THP1 cells after 18 hrs, EC50 = 0.01 μM.	17416521
RAW264.7	Function assay		24 hrs	Induction of [3H]cholesterol efflux in mouse RAW264.7 cells loaded with acetylated-LDL after 24 hrs, EC50 = 0.029 μM.	19717304
SH-SY5Y	Function assay		24 hrs	Agonist activity at human LXRbeta expressed in human SH-SY5Y cells co-transfected with Gal4-LBD after 24 hrs by luciferase reporter gene assay, EC50 = 0.13 μM.	19264481
SH-SY5Y	Function assay		24 hrs	Agonist activity at human LXRalpha expressed in human SH-SY5Y cells co-transfected with Gal4-LBD after 24 hrs by luciferase reporter gene assay, EC50 = 0.31 μM.	19264481
CHOK1	Function assay		24 hrs	Agonist activity at Gal4-tagged LXRbeta (unknown origin) expressed in CHOK1 cells after 24 hrs by luciferase reporter gene assay, EC50 = 0.42 μM.	25677664
CHOK1	Function assay		24 hrs	Agonist activity at Gal4-tagged LXRalpha (unknown origin) expressed in CHOK1 cells after 24 hrs by luciferase reporter gene assay, EC50 = 1.3 μM.	25677664
THP1	Function assay			Agonist activity at GAL-linked human LXRbeta expressed in THP1 cells assessed as stimulation of co-activator recruitment by FRET assay, EC50 = 0.027 μM.	17665897
COS7	Function assay			Activation of LXRbeta co-transfected in COS7 cells with RXRalpha by reporter transactivation assay, EC50 = 0.015 μM.	17416521
THP1	Function assay			Induction of cholesterol efflux in THP1 cells, EC50 = 0.01 μM.	17587573
THP1	Function assay			Stimulation of [3H]cholesterol efflux in human THP1 foam cells loaded with ac-LDL, EC50 = 0.031 μM.	18973288
CV1	Function assay			Antagonist activity at LXRbeta ligand binding domain assessed as inhibition of T1317-induced transcriptional activity in african green monkey CV1 cells co-transfected with Gal4-SRC1 by luciferase reporter assay, IC50 = 0.03981 μM.	20345102
THP1	Function assay			Agonist activity at GAL-linked human LXRalpha expressed in THP1 cells assessed as stimulation of coactivator recruitment by FRET assay, EC50 = 0.097 μM.	17665897
CV1	Function assay			Antagonist activity at LXRalpha ligand binding domain assessed as inhibition of T1317-induced transcriptional activity in african green monkey CV1 cells co-transfected with Gal4-SRC1 by luciferase reporter assay, IC50 = 0.1 μM.	20345102
HepG2	Function assay			Effect on SREBP1c gene expression in human HepG2 cells, EC50 = 0.21 μM.	18973288
HuH7	Function assay			Agonist activity at human recombinant LXRbeta ligand binding domain in human HuH7 cells co-transfected with fused Gal4-DBD by transactivation assay, EC50 = 0.31 μM.	18973288
CHO	Function assay			Agonist activity at human LXR beta receptor expressed in CHO cells by reporter assay, EC50 = 0.41 μM.	17034119
THP1	Function assay			Effect on ABCA1 gene expression in human differentiated THP1 cells, EC50 = 0.434 μM.	18973288
CV1	Function assay			Agonist activity at LXRbeta ligand binding domain-mediated transcriptional activity in african green monkey CV1 cells co-transfected with Gal4-SRC1 by luciferase reporter assay, EC50 = 0.50119 μM.	20345102
HuH7	Function assay			Agonist activity at human recombinant LXRalpha ligand binding domain in human HuH7 cells co-transfected with fused Gal4-DBD by transactivation assay, EC50 = 0.66 μM.	18973288
CV1	Function assay			Agonist activity at LXRalpha ligand binding domain-mediated transcriptional activity in african green monkey CV1 cells co-transfected with Gal4-SRC1 by luciferase reporter assay, EC50 = 0.79433 μM.	20345102
HepG2	Function assay			Effect on triglyceride accumulation in human HepG2 cells, EC50 = 2.002 μM.	18973288
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
点击查看更多细胞系数据

生物活性

产品描述

GW3965 HCl是一种有效的，选择性LXR激动剂，作用于hLXRα和hLXRβ，无细胞试验中EC50分别为190和30 nM。

靶点

hLXRβ ^[1] (Cell-free assay)	LXRα/SRC1 LiSA ^[1] (Cell-free assay)	hLXRα ^[1] (Cell-free assay)
30 nM(EC50)	125 nM(EC50)	190 nM(EC50)

体外研究(In Vitro)
体外研究活性	GW3965使类固醇受体共激活因子1聚集到LXRα，在无细胞配体检测试验中，EC50 为125 nM。^[1] GW3965对hLXRα 和 hLXRβ表现出有效的拮抗活性，在细胞试验中EC50分别为190 nM 和30 nM。此外，GW3965也对其他核受体表现出优良的选择性。^[1] 在人胰岛中，GW3965 (1 μM)降低选定促炎性细胞因子，包括IL-8，单核细胞趋化蛋白-1和组织因子的表达。^[4]
实验图片	检测方法	检测指标	实验图片	PMID
	Western blot	Skp2 / pEGFR / EGFR / pERK / ERK LXRα / LXRβ / ABCA1 / ABCG1		25184494
	Immunofluorescence	LAMP-1 / LDLR pRelA		23382078
	Growth inhibition assay	Cell viability		25184494

体内研究(In Vivo)
体内研究活性	在小鼠体内，GW3965在10 mg/kg剂量下使ABCA1表达上调8倍，并使循环水平提高30%，C_max为12.7 μg/mL ，t_1/2为2小时。^[1] 在LDLR−/−和apoE−/−小鼠体内，GW3965 (10mg/kg)诱导ABCA1 和ABCG1表达，并表现出有效的抗动脉粥样硬化活性。^[2] 在雄性sprague-dawley大鼠体内，GW3965降低Ang II介导的血压增加，并减少血管Ang II受体基因表达。^[3] 在恶性胶质瘤小鼠模型中，GW3965导致LDLR降解，增加ABCA1胆固醇外排转运体的表达，从而有效促进肿瘤细胞死亡。^[5]
动物实验	Animal Models	C57BL/6 小鼠
	Dosages	≤10 mg/kg
	Administration	口服

参考文献
[1] Collins JL, et al. J Med Chem. 2002, 45(10), 1963-1966. [2] Joseph SB, et al. Proc Natl Acad Sci U S A. 2002, 99(11), 7604-7609. [3] Leik CE, et al. Br J Pharmacol. 2007, 151(4), 450-456. [4] Scholz H, et al. Diabetologia. 2009, 52(7), 1352-1362. [5] Guo D, et al. Cancer Discov. 2011, 1(5), 442-456. [6] Di Conza G, et al. Nat Immunol. 2021 Nov;22(11):1403-1415. + 展开

参考文献

+ 展开

化学信息&溶解度

分子量	618.51	分子式	C₃₃H₃₁ClF₃NO₃.HCl
CAS号	405911-17-3	SDF	Download GW3965 HCl SDF
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
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

体外溶解度
批次：

DMSO : 100 mg/mL ( (161.67 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 50 mg/mL ( (80.83 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 33 mg/mL ( (53.35 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩尔浓度计算器

体内溶解度批次：现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂					动物体内配方计算器
体内溶解度批次：现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂	澄清溶液	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	5.0mg/ml (8.08mM)	以 1 mL 工作液为例,取50μL100mg/ml的澄清DMSO储备液加到400μLPEG300中,混合均匀使其澄清;向上述体系中加入50μLTween80,混合均匀使其澄清;然后继续加入500μLddH2O定容至1mL。工作液请现配现用!	动物体内配方计算器
澄清溶液	5% DMSO 1 95% Corn oil	0.6mg/ml (0.97mM)	以1 mL工作液为例，取50μL 12mg/ml的澄清DMSO储备液加到950μL玉米油中，混合均匀。工作液请现配现用！
澄清溶液	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	0.8mg/ml (1.29mM)	以 1 mL 工作液为例，取50μL16mg/ml的澄清DMSO储备液加到400μL PEG300中，混合均匀使其澄清；向上述体系中加入50μLTween80，混合均匀使其澄清；然后继续加入500μL ddH2O定容至 1 mL。工作液请现配现用！

实验计算

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×

稀释计算器分子量计算器

动物体内配方计算器（澄清溶液）

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 μL 动物数量只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

计算结果：

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH₂O，混匀澄清。

体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。

注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

技术支持

在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题，请给我们留言。

* 必填项

常见问题及建议解决方法

问题 1:
How to formulate the compound for mouse in vivo experiment?

回答：
S2630 GW3965 HCl can be dissolved in 2% DMSO/30% PEG 300/dd H2O at 10 mg/mL as a homogeneous suspension. This vehicle is suitable for oral gavage to mice.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):