生物活性
SAR439859 (Amcenestrant) is an orally active, nonsteroidal and selective degrader of estrogen receptor, it is also a potent antagonist of ER with EC50 of 0.2 nM for ERα degradation. SAR439859 has demonstrated broader and superior ER antagonist and degrader activities across a large panel of ER+ cells, including inhibition of ER signaling and tumor cell growth.
In vivo treatment with SAR439859 demonstrates significant tumor regression in ER+ breast cancer models, including MCF7-ESR1 wild-type and mutant-Y537S mouse tumors, and HCI013, a patient-derived tamoxifen-resistant xenograft tumor. SAR439859 (2.5-25 mg/kg; orally twice daily for 30 days) exhibits substantial tumor-growth inhibition and displays tumor regression at the dose of 25 mg/kg/BID.
化学数据
| 分子量 | 554.48 |
| 分子式 | C31H30Cl2FNO3 |
| CAS号 | 2114339-57-8 |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO 80 mg/mL |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | LCC2 cells, MCF7 cells |
| 方法 | Trypsinized cells are dispensed into 384-well plates in IMEM (supplemented with 5% FBS) and after overnight incubation cells are treated with SAR439859 for the times indicated. Cell viability is assessed using CellTiter-Glo according to the manufacturer’s protocol and relative luminescence units (RLU) are measured using an Envision Multilabel Reader. The RLUs of the treated samples are normalized to that of the untreated samples and cell viability is expressed as a percentage of the value of the untreated cells. |
| 浓度 | 0.01-1000 nM |
| 处理时间 | 7 days, 4 hours |
| 动物实验 |
|---|
| 动物模型 | Nu/nu mouse with MCF7 tumor xenograft model |
| 配制 | solution (0.6 mg/mL) in glycofurol/PS80/G5 (10%/5%/85%) and solution (1 mg/mL) in labrasol/solutol/G5 (20%/5%/75%) |
| 剂量 | 2.5, 5, 12.5, 25 mg/kg |
| 给药处理 | Orally; twice daily for 30 days |
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) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8035 mL | 9.0175 mL | 18.0349 mL |
| 5 mM | 0.3607 mL | 1.8035 mL | 3.607 mL |
| 10 mM | 0.1803 mL | 0.9017 mL | 1.8035 mL |
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