GNE-3500 (GNE3500) is a potent, selective, and orally bioavailable RORγ inhibitor with IC50 of 47 nM in IL-17 promoter assays.
GNE-3500 displays 75-fold selectivity over other ROR family members and >200-fold selectivity over 25 additional nuclear receptors.
GNE-3500 inhibits the production of all three IL-17 subtypes in murine CD4+ T cells with EC50 of 0.27-1.8 uM, also inhibits the production of IL-17AA and -AF by ILCs.
GNE-3500 shows in vitro ADME properties, in vivo PK, and dose-dependent inhibition of IL-17 in vivo.
