GDC-0810_Brilanestrant_ARN-810_Estrogen Receptor_CAS号1365888-06-7说明书_AbMole中国

分子量446.90

溶解性（25°C）DMSO ≥ 60 mg/mL

分子式C26H20ClFN2O2Water Insoluble

CAS号1365888-06-7Ethanol

储存条件3年 -20°C 粉末状

生物活性

GDC-0810对ER-α的降解和MCF-7细胞活性具有有效抑制作用，EC50和IC50分别为0.7 nM和2.5 nM。GDC-0810（Brilanestrant）对CYP2C8具有有效的抑制作用，IC50小于0.1 μM。GDC-0810对其他核激素受体的微弱作用说明其选择性良好。GDC-0810通过与雌激素受体结合而起作用，诱导构象变化，导致受体降解。

GDC-0810的药代动力学特征显示它具有良好的生物利用度（40%-60%）。作为亲脂性的羧酸，它能与血浆蛋白高度结合（>99.5%），具有低至中等的分布容积（Vss = 0.2?2.0 L/kg）。GDC-0810（3 mg/kg，po）在他莫昔芬?感的MCF-7异种移植模型中显示出显着的肿瘤生长抑制，而在100mg/kg/天的最高剂量下，所有动物显示肿瘤消退超过50%。

实验操作来自于公开的文献，仅供参考

细胞实验

细胞系MCF-7 cells

方法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 ?nal 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).

浓度

处理时间 5 days

动物实验

动物模型tamoxifen-sensitive MCF-7 xenograft model

配制PEG400/PVP/TW80/0.5% CMC in water, 9:0.5:0.5:90

剂量30 and 100 mg/kg

给药处理p.o.

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

小鼠大鼠兔豚鼠仓鼠狗

重量 (kg)0.020.15 1.80.40.0810

体表面积 (m)0.0070.0250.150.050.020.5

K系数36128520

动物 A (mg/kg) = 动物 B (mg/kg) × 动物 B的K系数动物 A的K系数

GDC-0810 目录号M8953

化学数据

2

m

m

m

例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的K系数（3），再除以大鼠的K系数

m m （6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。

参考文献

The selective estrogen receptor downregulator GDC-0810 is e?cacious in diverse models of ER+ breast cancer.

Joseph JD, et al. Elife. 2016 Jul 13;5. pii: e15828. PMID: 27410477.

Identi?cation of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.

Lai A, et al. J Med Chem. 2015 Jun 25;58(12):4888-904. PMID: 25879485.