XY018

**XY018** is a chemically defined, orally available, selective and potent small molecule antagonist of Retinoic acid-related orphan receptor gamma (ROR-γ)[1][3][7][11][14]. ROR-γ is a nuclear receptor involved in transcriptional regulation of genes responsible for cholesterol synthesis, immune function, gluconeogenesis, and cancer cell survival[9][2][12]. XY018 shows strong antitumor activity by inhibiting ROR-γ signaling, resulting in potent inhibition of growth and survival in a broad range of cancer cell types, including breast, lung, ovarian, bladder, endometrial, liver, glioblastoma, lymphoma, colon, and docetaxel-resistant prostate cancer cells[7][9][11][12]. It also sensitizes tamoxifen-resistant breast cancer cells to tamoxifen[7]. In metabolic disease models, XY018 improves glucocorticoid-induced glucose intolerance and reduces hepatic gluconeogenesis by suppressing transcriptional activity at genes like Pck1 and G6pc1[2]. XY018 demonstrates a favorable selectivity profile for ROR-γ over other nuclear receptors[8]. It is being developed for cancer and metabolic indications.

Brand names

XY018XY-018XY 018

Other names

XY018XY-018XY 018