LG100754 (UVI 2112) is a specific antagonist of RXR homodimer, also functions as a RXR:PPARα and RXR:PPARγ agonist. LG100754 does not activate other heterodimers like RXR:liver X receptoralpha, RXR:liver X receptorbeta, RXR:bile acid receptor/farnesoid X receptor and RXR:nerve growth factor induced gene B. LG100754 triggers cellular RXR:PPARgamma-dependent pathways including adipocyte differentiation and inhibition of TNFalpha-mediated hypophosphorylation of the insulin receptor, but does not activate key farnesoid X receptor and liver X receptor target genes. LG100754 treatment of db/db animals leads to an improvement in insulin resistance in vivo. LG100754 sensitizes the potency of proliferator-activated receptor (PPAR) gamma-retinoid X receptor heterodimers for PPARgamma ligands.
