XY101 is a potent, selective, metabolically stable and orally available RORγ inverse agonist with an IC50 of 30 nM and a Kd of 380 nM[1].
IC50 & Target
IC50: 30 nM (RORγ)[1] Kd: 380 nM (RORγ)[1]
体外研究 (In Vitro)
XY101 potently inhibits cell growth, colony formation, and the expression of androgen receptor (AR), AR-V7 and prostate-specific antigen (PSA)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
XY101 exhibits significant antitumor activities during the treatment period with tumor growth inhibition and is well tolerated without obvious body weight loss[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
563.48
Formula
C25H20F7NO4S
CAS 号
2349368-16-5
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Zhang Y, 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.
XY1 is a very close analogue of SGC707 (a potent, selective, and non-competitive inhibitor of PRMT3 with IC50 of 31 nM), but XY1 is completely inactive. Target: PRMT3 XY1 is a close analogue of SGC707, is completely inactive againstPRMT3 at concentrations as high as 100 μM. XY1 contains a naphthyl group replacing the isoquinoline group, lacks the key hydrogen bond with T466. The naphthyl ring of XY1 could act as a weak hydrogen-bond acceptor, but this should come with a substantial enthalpic penalty. The more than 1000-fold potency loss of XY1 compared with SGC707 supports this analysis. It is unclear whether other factors such as electronic effects also contributed to the potency loss of XY1 compared with SGC707. SGC707 and XY1 are a pair of excellent tools for the biomedical community to further elucidate biological functions and disease associations of PRMT3.
Clinical Trial
分子量
297.35
Formula
C17H19N3O2
CAS 号
1624117-53-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Kaniskan H?, et al. A potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3). Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5166-70.
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].
IC50 & Target[1][2]
ROR-γ
0.19 μM (IC50, in 293 T cells)
ROR-α
7.57 μM (IC50, in 293 T cells)
体外研究 (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 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].
上海金畔生物科技有限公司 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.
体内研究 (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].
上海金畔生物科技有限公司 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
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.
分子量
516.37
Formula
C23H15F7N2O4
CAS 号
1873358-87-2
运输条件
Room temperature in continental US; may vary elsewhere.
[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.
XY-06-007 is a selective and potent bump-and-hole (B&H)-PROTAC BRD4BD1L94V degrader. XY-06-007 shows a DC50, 6 h of 10 nM against BRD4BD1L94V with no degradation of off-targets. XY-06-007 demonstrates suitable pharmacokinetics for in vivo studies[1].
IC50 & Target
Cereblon
体外研究 (In Vitro)
XY-06-007 shows a half-degradation concentration (DC50, 6 h) of 10.2±1.8 nM against BRD4BD1L94V with no degradation of off-targets, as assessed by whole proteome mass spectrometry[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
XY-06-007 has favorable pharmacokinetic profile, including good plasma concentration, area under the curve (AUC), and bioavailability. XY-06-007 exhibits short elimination half-life (0.515 h) due to relatively low clearance (21.9 mL/min/kg) following intravenous administration (2.0 mg/kg). XY-06-007 exhibits short elimination half-life (0.721 h) due to the Cmax (6.10 μM) and Tmax (0.25 h) following intraperitoneal injection (10 mg/kg)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Six to eight weeks old male C57BL/6 mice[1]
Dosage:
2 mg/kg (iv) or 10 mg/kg (ip) (Pharmacokinetic Analysis)
Administration:
Administered via tail vein injection or via intraperitoneal injection. Approximately 110 μL of blood/time point was collected into the K2EDTA tube via facial vein for bleeding for the time points: 0.083, 0.25, 0.5, 1, 2, 4, 8, and 24 h.
Result:
Maintained above its DC50, 6h of 10 nM for approximately 6 h when dosed at 10 mg/kg via intraperitoneal injection (IP), indicating that such in vivo degradation experiment would result in a favorable outcome.
分子量
809.27
Formula
C41H41ClN8O8
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
溶解性数据
In Vivo:
1.
XY-06-007 is formulation: 0.4 mg/mL 5% DMSO + 5% solutol HS15 + 90% saline for vein injection (iv). XY-06-007 is formulation: 1.0 mg/mL 5% DMSO + 5% solutol HS15 + 90% saline for intraperitoneal injection (ip)[1].
参考文献
[1]. Radosław P Nowak, et al. Structure-Guided Design of a “Bump-and-Hole” Bromodomain-Based Degradation Tag. J Med Chem. 2021 Aug 12;64(15):11637-11650.
XY028-140 is a PROTAC connected by ligands for Cereblon and CDK. XY028-140 inhibits both CDK4/6 expression and CDK4/6 activity in cancer cells[1].
IC50 & Target[1]
CDK4
CDK6
Cereblon
体外研究 (In Vitro)
A375 melanoma and T47D breast cancer cells are treated with 0.3 or 1 µΜ XY028-140 for 24 hours. XY028-140 inhibits both CDK4/6 expression and CDK4/6 activity[1]. T47D breast cancer cells are treated with 0.03, 0.1, 0.3, 1, or 3 µΜ XY028-140 for 11 days. XY028-140 inhibits cancer cell proliferation in breast cancer cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
760.80
Formula
C39H40N10O7
CAS 号
2229974-83-6
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 5.56 mg/mL (7.31 mM; ultrasonic and warming and heat to 60°C)
