Novel RORg inverse agonists do not modulate androgen receptor activity in prostate cancer

Work published by Wang et al. described pharmacological inhibition of RORg with an inverse agonist (SR2211) which led to a decrease in AR gene expression and a reduction in AR protein, which led to the loss of an AR gene expression signature. We have developed a novel, specific, RORg inverse agonist (AZ RORgi) and have studied its effects on the transcriptome of LNCAP cell lines following 24 & 48 hours of treatment. We compare this to SR2211 as well as Enzalutamide, an AR antagonist. We show that Enzalutamide and SR2211 primarily act via the androgen receptor, whereas AZ RORgi does not modulate gene expression in these cell lines.