XY018

Research use only, not for human use.

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.

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).

XY018 (0.07-10 μM; 4 days) inhibit CRPC tumors C4-2B cells growth and survival.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. 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.Cell Viability Assay Cell Line:CRPC tumors C4-2B Concentration:0.07, 0.15, 0.31, 0.62, 1.25, 2.5, 5, and 10 μM Incubation Time:4 days Result:Inhibited growth and survival.

XY018 (5 mg/kg; intraperitoneally i.p.; five times per week for 23 days) inhibit CRPC tumor growth in mice. XY018 (10 mg/kg orally or 2 mg/kg intravenously) exhibits reasonable pharmacokinetics profiles in SD rats.Animal Model:Four-week-old male SCID C.B17 mice (for C4-2B and VCaP) or BALB/c nu/nu athymic mice (for 22Rv1 and PC-3)Dosage:5 mg/kg Administration:Treated intraperitoneally (i.p.); five times per week for 23 daysResult:Tumor growth inhibition.Animal Model:Sprague Dawley rats Dosage:10 mg/kg (po; 1 mg/mL); 2 mg/kg (iv;0.4 mg/mL) (Pharmacokinetic Analysis)Administration:Orally administrated (10 mg/kg) and intravenously administrated (2 mg/kg); single dose Result:High plasma exposure AUC(0–∞) value of 6444 (μg/L·h), half-life (T1/2=7.67±2.36 h) and maximum plasma concentration (Cmax) value of 839 (μg/L) after a 2 mg/kg iv administration.Demonstrated a relatively low oral bioavailability of 19% after an oral administration.

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Nuclear Receptor/Transcription Factor

ROR

ROR

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1873358-87-2

516.37

C23H15F7N2O4

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (193.66 mM; Ultrasonic )

O=C(CC1=C([N+]([O-])=O)C=CC=C1)NC2=CC=C(C3=CC=C(C(C(F)(F)F)(C(F)(F)F)O)C=C3F)C=C2

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(-20℃)

With Ice Pack

≥ 2 years