[CAS NO. 1873358-87-2] XY018
PRODUCTS SPECIFICATIONS [1873358-87-2]
DESCRIPTION [1873358-87-2]
Overview
| MDL | MFCD31656707 |
|---|---|
| Molecular Weight | 516.37 |
| Molecular Formula | C23H15F7N2O4 |
| SMILES | OC(C(F)(F)F)(C1=CC(F)=C(C(C=C2)=CC=C2NC(CC(C=CC=C3)=C3[N](=O)=O)=O)C=C1)C(F)(F)F |
Summary
XY018 is a potent ROR-γ -selective antagonist. XY018 inhibits ROR-γ constitutive activity in 293T cells with high potency ( EC 50 , 190 nM). XY018 binds to the ROR-γ hydrophobic ligand binding domain (LBD) [1] .
IC50 & Target
|
ROR-γ 0.19 μM (IC 50 , in 293 T cells) |
ROR-α 7.57 μM (IC 50 , in 293 T cells) |
In Vitro
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 IC
50
s 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 IC
50
s of 5.14±0.36, 9.00±0.33, 9.20, 28.43±0.89, and 11.14±1.78 μM, respectively
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| 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. |
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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) [1] |
| Dosage: | 5 mg/kg |
| Administration: | Treated intraperitoneally (i.p.); five times per week for 23 days |
| Result: | Tumor growth inhibition. |
| Animal Model: | Sprague Dawley rats [2] |
| 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 (T
1/2
=7.67±2.36 h) and maximum plasma concentration (C
max
) value of 839 (μg/L) after a 2 mg/kg iv administration.
Demonstrated a relatively low oral bioavailability of 19% after an oral administration. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 193.66 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9366 mL | 9.6830 mL | 19.3660 mL |
| 5 mM | 0.3873 mL | 1.9366 mL | 3.8732 mL |
| 10 mM | 0.1937 mL | 0.9683 mL | 1.9366 mL |
References
- [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.
