| CAS |
No.1365888-06-7 |
| 英文名称 |
Brilanestrant |
| 别名 |
ARN-810 |
| 分子式 |
C26H20ClFN2O2 |
| 分子量 |
446.9 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD28902190 |
| SMILES |
O=C(O)/C=C/C1=CC=C(/C(C2=CC3=C(NN=C3)C=C2)=C(C4=CC=C(F)C=C4Cl)/CC)C=C1 |
| 靶点 |
Estrogen Receptor/ERR |
| 通路 |
Endocrinology & Hormones |
| 背景说明 |
是一种有效的ER-α结合剂,是其转录拮抗剂,而非激活作用。 |
| 生物活性 |
Brilanestrant (ARN-810; GDC-0810) is an orally bioavailable selective estrogen receptor degrader (SERD) with IC50 of 0.7 nM.[1-2] |
| IC50 |
IC50: 0.7 nM (estrogen receptor)[1-2] |
| In Vitro |
Brilanestrant (ARN-810; GDC-0810) is a potent ER-α binder (IC50=6.1 nM)， a full transcriptional antagonist with no agonism (3× ERE， IC50=2 nM)， and displays good potency and efficacy in ER-α degradation (EC50=0.7 nM) and MCF-7 breast cancer cell viability (IC50=2.5 nM) assays[1].Brilanestrant (ARN-810; GDC-0810) induces a distinct ERα conformation versus tamoxifen and other ER therapeutics， and does not exhibit tamoxifen-like ER agonism in MCF7 cells[2]. |
| In Vivo |
The pharmacokinetic profile of Brilanestrant (ARN-810) shows it is a olw clearance molecule across species， with good bioavailability (40%-60%). Brilanestrant (ARN-810) (3 mg/kg， p.o.) shows substantial tumor-growth inhibition in a tamoxifen-sensitive MCF-7 xenograft model， while at the highest dose of 100 mg/kg/day， all animals show tumor regression of more than 50% without weight loss[1].Brilanestrant (ARN-810) exhibits low clearance (11 mL/min/kg) and 61% oral bioavailability. Brilanestrant (ARN-810) (1-100 mg/kg/day， p.o.) displays dose dependent efficacy in the MCF7 xenograft model[2]. |
| 细胞实验 |
MCF-7 cells are adjusted to a concentration of 40000 cells per mL in RPMI containing 10% FBS and 20 mM HEPES. Then 16 μL of the cell suspension (640 cells) is added to each well of a 384-well plate， and the cells are incubated overnight to allow the cells to adhere. The following day a 10-point， serial 1:5 dilution of each compound is added to the cells in 16 μL at a final concentration ranging from 10 to 0.000005 μM. After 5 days‘ compound exposure， 16 μL of CellTiter-GLo is added to the cells， and the relative luminescence units of each well are determined. CellTiter-GLo added to 32 μL of medium without cells is used to obtain a background value. The percent viability of each sample is determined as follows: (RLU sample-RLU background/RLU untreated cells-RLU background ×100=%viability) |
| 动物实验 |
Time release pellets containing 0.72 mg 17-β estradiol are subcutaneously implanted into nu/nu mice. MCF-7 cells are grown in RPMI containing 10% FBS at 5% CO2 37°C. Trypsinized cells are pelleted and resuspended in 50% RPMI（serum free）and 50% Matrigel at 1×107 cells/mL. MCF-7 cells are subcutaneously injected (100 μL/animal) on the right flank 2-3 days post pellet implantation. Tumor volume (length × width2/2) is monitored biweekly. When tumors reach an average volume of appr 200 mm3 animals are randomized and treatment is started. Animals are treated with vehicle or compound daily for 4 weeks. Tumor volume and body weight are monitored biweekly throughout the study. |
| 数据来源文献 |
[1]. By Lai， et al. Identification of GDC-0810 (ARN-810)， an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts. J Med Chem. 2015 Jun 25;58(12):4888-904.
[2]. Joseph JD， et al. The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer. Elife. 2016 Jul 13;5. pii: e15828. doi: 10.7554/eLife.15828 |
| 规格 |
2mg 5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
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