WO95E is a novel potent, synthetic ligand (partial agonist) of PPARγ, directly binds to PPARγ with IC50 of 11 nM;
WO95E's binding affinity is approximately 70-fold lower than that of UHC1 (Journal of Biological Chemistry. 2014;289(38):26618–26629.).
WO95E significantly inhibited the S273 phosphorylation of PPARγ in 3T3-L1 differentiated adipocytes, led to the upregulation of the mRNA levels of a number of the PPARγ phosphorylation-dependent genes, including adiponectin, cycp2f2, Ddx-17, Rarres2, and Selenbp1.
Unlike SR1664 and UHC1, WO95E does not bind to the canonical PPARγ ligand-binding pocket (LBP) containing H3, H3-4 loop, H11 and H12, which full agonist Rosi binds, instead, WO95E binds to the ABP comprising H2′-H3, β-sheet, and the Ω loop.
WO95E improved glucose tolerance and insulin sensitivity in DIO mice.
