GW3965 HCl

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

GW3965 HCl Chemical Structure

CAS No. 405911-17-3

Purity & Quality Control

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

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation 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 Cmax of 12.7 μg/mL and t1/2 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.

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)

In vitro
Batch:

DMSO : 124 mg/mL ( (200.48 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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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. )

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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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