XY018 is an orally available, selective and highly effective ROR-γ antagonist with antitumor activity, inhibits ROR-γ activity, inhibits tumor cell growth, and can be used to study drug-resistant prostate cancer.

RORγ:0.19 μM (PME-1 (HEK293T)), RORα:7.57 μM (PME-1 (HEK293T))

METHODS: C4-2B cells were treated with XY018 (0.07, 0.15, 0.31, 0.62, 1.25, 2.5, 5, 10 μM for 4 days), the cell titer GLO reagent was added, and cell viability was measured by luminescence on a GLOMAX microplate luminometer according to the manufacturer's instructions.
RESULTS:XY018 inhibited the growth and survival of C4-2B cells. [1]

METHODS: XY018 (5 mg/kg, intraperitoneal injection, 5 times a week for 23 days) was used to treat xenograft tumor model mice generated using PCa cell lines with different characteristics (such as C4-2B expressing AR with mutant LBD, VCaP and AR-V7 with amplified AR genes, 22Rv1 expressing high levels of multiple AR variants, and AR-negative PC3), and tumor growth in mice was observed.
RESULTS:XY018 inhibited CRPC tumor growth in mice. [1]
METHODS: XY018 (10 mg/kg, oral; 2 mg/kg, intravenous) was used to treat SD rats and its pharmacokinetic characteristics were determined.
RESULTS:XY018 showed good pharmacokinetic characteristics in rats, with the same bioavailability of 19%, and an intravenous half-life of 7.67 hours. [2]