In vitro activity: DY131 (also known as GSK-9089) is a novel selective agonist at estrogen-related receptors ERRβ and ERRγ with minimal activity at ERRα, ERα and ERβ at concentrations up to 30 μM. DY131 inhibited the growth of the ERα-positive endometrial cancer cells but promoted that of the ERα-negative cancer cells. DY131 had no effect on the structurally related receptors ERRα or the estrogen receptors alpha and beta (ERalpha/beta). By targeting ERRgamma, DY131 could be a novel therapeutic for prostate cancer treatment.

Kinase Assay:

Cell Assay: ERRβ/γ DY131, a selective ERRγ agonist, could potentiate the ERRγ-induced growth inhibition in LNCaP- ERRγ and DU145- ERRγ cells in a dose-dependent manner compared with respective parental cells. DY131 inhibited the growth of the ERα-positive endometrial cancer cells but promoted that of the ERα-negative cancer cells. DY131 had no effect on the structurally related receptors ERRα or the estrogen receptors alpha and beta (ERalpha/beta). DY131 appears to inhibit Smo signaling through a common binding site shared by previously reported Smo agonists and antagonists.