GW3965 hydrochloride

• Catalog No.: S2630
• CAS Number: 405911-17-3
• M. F.: C33H32Cl2F3NO3
• M. W.: 618.5132896
• Storage: -20°C

SYNONYMS

• IUPAC name: 2-{3-[3-({[2-chloro-3-(trifluoromethyl)phenyl]methyl}(2,2-diphenylethyl)amino)propoxy]phenyl}acetic acid hydrochloride
• IUPAC Traditional name: C33H31ClF3NO3 hydrochloride
• Synonyms: GW-3965

DATABASE IDS

• CAS Number: 405911-17-3

PROPERTIES

• Target: liver X receptor (LXR)
• Salt Data: HCL
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: GW3965 is a potent, selective LXR agonist, which exhibits its potency in the LXRα/SRC1?LiSA and LXRα-GAL4 with EC50 of 125 nM and 190 nM, respectively.
• Targets: LXRα/SRC1?LiSA; LXRα-GAL4; LXRβ
• IC50: 125 nM ^[1]; 190 nM ^[1]; 30 nM ^[1]
• 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]
• 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]

Protocol

• Protocol: Animal Study ^[1]
• Animal Models: C57BL/6 mice
• Formulation: GW3965 is dissolved in 0.5% Methyl Cellulose.
• Doses: ≤10 mg/kg
• Administration: Administered via p.o.

References

• References: [1] Collins JL, et al. J Med Chem. 2002, 45(10), 1963-1966.
• References: [2] Joseph SB, et al. Proc Natl Acad Sci U S A. 2002, 99(11), 7604-7609.
• References: [3] Leik CE, et al. Br J Pharmacol. 2007, 151(4), 450-456.
• References: [4] Scholz H, et al. Diabetologia. 2009, 52(7), 1352-1362.
• References: [5] Guo D, et al. Cancer Discov. 2011, 1(5), 442-456.

REFERENCES

• Collins JL, et al. J Med Chem. 2002, 45(10), 1963-1966.
• Joseph SB, et al. Proc Natl Acad Sci U S A. 2002, 99(11), 7604-7609.
• Leik CE, et al. Br J Pharmacol. 2007, 151(4), 450-456.
• Scholz H, et al. Diabetologia. 2009, 52(7), 1352-1362.
• Guo D, et al. Cancer Discov. 2011, 1(5), 442-456.