GW3965

• CAT Number: I003478
• CAS Number: 405911-09-3
• Molecular Formula: C33H31ClF3NO3
• Molecular Weight: 582.05
• Purity: ≥95%
• Synonyms: 2-[3-[3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]propoxy]phenyl]acetic acid
• Target: LXR
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 190/30 nM (hLXRα/β)

GW3965 is a potent, selective LXR agonist for hLXRα and hLXRβ with EC50 of 190 and 30 nM, respectively.IC50 value: 190/30 nM (hLXRα/β)Target: LXRGW3965 has an EC50 = 125 nM in a cell-free ligand-sensing assay of LXRα and profiles as a full agonist on hLXRα and hLXRβ in cell-based assays with EC50 = 190 nM and 30 nM, respectively. Angiotensin II-mediated increases in blood pressure can be reduced by GW3965 hydrochloride. In HepG2 cells, the EC50 for GW3965 is greater than 4 μM. In an animal study, GW3965 hydrochloride decreased lesion area by 53% 34% in male and female LDLR-/- mice, respectively. GW3965 induced expression of ATP-binding cassettes A1 and G1 in modified low-density lipoprotein-loaded macrophages in vitro as well as in the aortas of hyperlipidemic mice. Additionally, GW3965 hydrochloride increases ABCA1 gene expression and raises circulating HDL levels. GW3965 hydrochloride displays potent antiatherogenic activity in mouse models of atherosclerosis.

Reference

[1]. Mitro, Nico; Cermenati, Gaia; Giatti, Silvia et al. LXR and TSPO as new therapeutic targets to increase the levels of neuroactive steroids in the central nervous system of diabetic animals. Neurochemistry International (2012), 60(6), 616-621.
[2]. Guo, Deliang; Reinitz, Felicia; Youssef, Mary et al. An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR-Dependent Pathway. Cancer Discovery (2011), 1(5), 442-456.
[3]. Spyridon, Michael; Moraes, Leonardo A.; Jones, Chris I. et al. LXR as a novel antithrombotic target. Blood (2011), 117(21), 5751-5761.
[4]. Donkin, James J.; Stukas, Sophie; Hirsch-Reinshagen, Veronica et al. ATP-binding Cassette Transporter A1 Mediates the Beneficial Effects of the Liver X Receptor Agonist GW3965 on Object Recognition Memory and Amyloid Burden in Amyloid Precursor Protein/Presenilin 1 Mice. Journal of Biological Chemistry (2010), 285(44), 34144-34154.
[5]. Leik, C. E.; Carson, N. L.; Hennan, J. K. et al. GW3965, a synthetic liver X receptor (LXR) agonist, reduces angiotensin II-mediated pressor responses in Sprague-Dawley rats. British Journal of Pharmacology (2007), 151(4), 450-456.