| Bioactivity | XY018 is a potent ROR-γ-selective antagonist. XY018 inhibits ROR-γ constitutive activity in 293T cells with high potency (EC50, 190 nM). XY018 binds to the ROR-γ hydrophobic ligand binding domain (LBD)[1]. | ||||||||||||
| Invitro | XY018 (0.07-10 μM; 4 days) inhibit CRPC tumors C4-2B cells growth and survival[1].XY018 inhibits Gal4-RORγ-LBD and Gal4-RORα-LBD with IC50s of 0.19±0.02 and 7.57 μM in 293 T cells, respectively[2]. XY018 shows anti-proliferation effects against the prostate cancer cell lines LNCaP, 22Rv1, C4-2B, DU145, and PC-3 with IC50s of 5.14±0.36, 9.00±0.33, 9.20, 28.43±0.89, and 11.14±1.78 μM, respectively[2]. Cell Viability Assay[1] Cell Line: | ||||||||||||
| In Vivo | XY018 (5 mg/kg; intraperitoneally i.p.; five times per week for 23 days) inhibit CRPC tumor growth in mice[1] . XY018 (10 mg/kg orally or 2 mg/kg intravenously) exhibits reasonable pharmacokinetics profiles in SD rats[2]. Animal Model: | ||||||||||||
| Name | XY018 | ||||||||||||
| CAS | 1873358-87-2 | ||||||||||||
| Formula | C23H15F7N2O4 | ||||||||||||
| Molar Mass | 516.37 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Junjian Wang, et al. ROR-γ Drives Androgen Receptor Expression and Represents a Therapeutic Target in Castration-Resistant Prostate Cancer. Nat Med. 2016 May;22(5):488-96. [2]. Yan Zhang, et al. Discovery and Characterization of XY101, a Potent, Selective, and Orally Bioavailable RORγ Inverse Agonist for Treatment of Castration-Resistant Prostate Cancer. J Med Chem. 2019 May 9;62(9):4716-4730. |