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GW3965 HCl

Name: GW3965 HCl
Brand: Selleck Chemicals
SKU: S2630
Rating: 5 (46 reviews)

Catalog No.S2630 Purity:99.88%

GW3965 HCl is a potent, selective LXR agonist for hLXRα and hLXRβ with EC50 of 190 and 30 nM in cell-free assays, respectively.

GW3965 HCl Chemical Structure

CAS No. 405911-17-3

Purity & Quality Control

Batch: Purity: 99.88%

99.88

Products often used together with GW3965 HCl

Navitoclax (ABT-263)

GW3965 and Navitoclax (ABT-263) combination treatment reduces tumor growth significantly stronger than either drug alone in A375 xenograft model.

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

GW3965 HCl Related Products

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Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
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
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
THP1	Function assay			Induction of cholesterol efflux in THP1 cells, EC50 = 0.01 μM.	17587573
THP1	Function assay		18 hrs	Induction of cholesterol efflux in THP1 cells after 18 hrs, EC50 = 0.01 μM.	17416521
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
COS7	Function assay			Activation of LXRbeta co-transfected in COS7 cells with RXRalpha by reporter transactivation assay, EC50 = 0.015 μM.	17416521
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
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
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
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
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
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
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
CHO	Function assay			Agonist activity at human LXR beta receptor expressed in CHO cells by reporter assay, EC50 = 0.41 μM.	17034119
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
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
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
HepG2	Function assay			Effect on triglyceride accumulation in human HepG2 cells, EC50 = 2.002 μM.	18973288
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
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
Click to View More Cell Line Experimental Data

Biological Activity

Description

GW3965 HCl is a potent, selective LXR agonist for hLXRα and hLXRβ with EC50 of 190 and 30 nM in cell-free assays, respectively.

Targets

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)

In vitro
In vitro	GW3965 recruits the steroid receptor coactivator 1 to human LXRα with EC50 of 125 nM in a cell-free ligand-sensing assay. ^[1] GW3965 shows a potent antagonistic activity against hLXRα and hLXRβ in cell-based assays with EC50 of 190 nM and 30 nM, respectively. Besides, GW3965 also sows excellent selectivity over other nuclear receptors. ^[1] In human islets, GW3965 (1 μM) reduces expression of selected pro-inflammatory cytokines including IL-8, monocyte chemotactic protein-1 and tissue factor. ^[4]
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	LXRα / LXRβ / ABCA1 / ABCG1 Skp2 / pEGFR / EGFR / pERK / ERK		11604492
	Immunofluorescence	pRelA LAMP-1 / LDLR		26635040
	Growth inhibition assay	Cell viability		25184494

In Vivo
In vivo	In mice, GW3965 at a dose of 10 mg/kg upregulates ABCA1 expression 8-fold and raises circulating levels of HDL by 30% with C_max of 12.7 μg/mL and t_1/2 of 2 hours. ^[1] GW3965 (10mg/kg) induces expression of ABCA1 and ABCG1 and shows potent antiatherogenic activity in both LDLR−/− and apoE−/− mice. ^[2] In male sprague-dawley rats, GW3965 reduces Ang II-mediated increases in blood pressure and decreases vascular Ang II receptor gene expression. ^[3] In Glioblastoma mouse model, GW3965 results in inducible degrader of LDLR-mediated LDLR degradation, increased expression of the ABCA1 cholesterol efflux transporter, and thus potently promotes tumor cell death. ^[5]
Animal Research	Animal Models	C57BL/6 mice
	Dosages	≤10 mg/kg
	Administration	Administered via p.o.

References

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Chemical Information & Solubility

Molecular Weight	618.51	Formula	C₃₃H₃₁ClF₃NO₃.HCl
CAS No.	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
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (161.67 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (8.08mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.600mg/ml (0.97mM)	Taking the 1 mL working solution as an example, add 50 μL of 12 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.800mg/ml (1.29mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 16 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

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

Answer:
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.

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