product name GW3965 HCl
Description: GW3965 HCl is a potent, selective LXR agonist for hLXRα and hLXRβ. In cell-based reporter gene assays, GW3965 plays as a full agonist on hLXRα and hLXRβ with EC50 of 190 and 30 nM, respectively. GW3965 suppresses 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.
References: J Med Chem. 2002 May 9;45(10):1963-6; Proc Natl Acad Sci U S A. 2002 May 28;99(11):7604-9.
618.51
Formula
C33H31ClF3NO3.HCl
CAS No.
405911-17-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 16 mg/mL (25.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: GW3965 recruits the steroid receptor coactivator 1 to human LXRα with EC50 of 125 nM in a cell-free ligand-sensing assay. 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. In human islets, GW3965 (1 μM) reduces expression of selected pro-inflammatory cytokines including IL-8, monocyte chemotactic protein-1 and tissue factor. Kinase Assay: Cell Assay: |
|---|---|
| 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. GW3965 (10mg/kg) induces expression of ABCA1 and ABCG1 and shows potent antiatherogenic activity in both LDLR−/− and apoE−/− mice. In male sprague-dawley rats, GW3965 reduces Ang II-mediated increases in blood pressure and decreases vascular Ang II receptor gene expression. 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. |
| Animal model | C57BL/6 mice |
| Formulation & Dosage | Dissolved in 0.5% Methyl Cellulose; ≤10 mg/kg; oral gavage |
| References | J Med Chem. 2002 May 9;45(10):1963-6; Proc Natl Acad Sci U S A. 2002 May 28;99(11):7604-9. |
