ERα (IC50 = 48 nM), ERβ (IC50 = 870 nM)[1]

Elacestrant (RAD1901；0.5 nM-10 µM；48 h) 以浓度依赖性方式抑制 MCF-7 细胞中 ERα 的表达 (EC50 = 0.6 nM)[1]。 Elacestrant（0-1 µM；48 小时）以浓度依赖性方式对雌二醇 (E2) 刺激的 ER 阳性 MCF-7 细胞表现出抗增殖作用 (EC50 = 4 pM) [1]。 MCF7、T47D 中的 Elacestrant（0-1 µM；24 或 48 小时） Elacestrant（0.01、0.1、1.0 µM）可降低 MCF7 和 T47D 细胞系中孕酮受体（PGR、PR；ER 靶基因）的表达 [2] 。

Elacestrant（0.3-120 mg/kg；口服；每天一次，持续 40 天）以剂量依赖性方式抑制 E2 介导的智力刺激 [1]。 Elacetrant（30、60 mg/kg；口服；每天 10 天）。即使停药后，elelastrant 仍能阻止肿瘤生长[2]。

体外结合试验[2]
根据制造商的说明，在PolarScreen ERα竞争对手分析中，使用野生型和突变型ERα的纯化配体结合结构域测定依拉司琼的体外结合亲和力。

细胞增殖测定 [1]
细胞类型： ER 阳性 MCF-7 细胞（雌二醇 (E2) 刺激）[1]
测试浓度： 0-1 μM
孵育时间：48 小时
实验结果：证明对细胞具有抗增殖活性。 。

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蛋白质印迹分析[1]
细胞类型： MCF-7 细胞
测试浓度： 0.5 nM-10 µM
孵育持续时间：48小时
实验结果：以剂量依赖性方式抑制ERα表达（EC50为0.6 nM）。

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蛋白质印迹分析[2]
细胞类型： MCF7、T47D 和 HCC1428 细胞
测试浓度： 0-1 µM
孵化持续时间：24或48小时
实验结果：雌激素受体蛋白表达减少。

Animal/Disease Models: Mouse MCF7 cell line xenograft model [2].
Doses: 30, 60 mg/kg
Route of Administration: Oral; one time/day for 4 weeks
Experimental Results: Inhibition of tumor growth.

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In vivo xenograft experiments[2]
Female athymic nude mice (NU(NCr)-Foxn1nu or BALB/cAnNCrl-Foxn1nu) were acclimated for 3 to 7 days prior to implantation. Mice were given water (reverse osmosis, 1 ppm Cl) and fed a daily complete diet ad libitum, and were housed on irradiated bedding on a 12- to 14-hour light cycle under controlled temperature and humidity. Preformulated, clinical-grade fulvestrant (Faslodex) was obtained through third party vendors and administered by subcutaneous injection once weekly. Elacestrant, palbociclib and everolimus were administered daily by oral gavage. In the ST941 study, groups receiving palbociclib were initially administered 100 mg/kg and dose reduced to 75 mg/kg on day 14 of treatment. At the end of this study, average body weight loss for all treatment groups did not exceed 15%.

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MCF-7 xenografts.[2]
Twenty-four hours prior to implantation of MCF-7 cells, estrogen pellets (0. 18 mg/pellet 17β−estradiol, 90-day release) were implanted subcutaneously between the scapulae of female athymic nude mice using a sterilized trochar. MCF7 cells (5 × 106 per mouse) in 50:50 Matrigel:MEM were implanted in the rear flank. When mean tumor volumes reached approximately 150 to 200 mm3, mice were randomized to treatment groups based on tumor size. For pharmacodynamic analyses, MCF7 xenograft-bearing mice were treated daily for seven days, animals were euthanized, and tumors collected 4 and 24 hours post-last dose.

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Patient-derived xenograft models.[2]
HBCx-21, HBCx-3 and HBCx-19 patient-derived tumor xenografts (PDX) were derived at and studies run at XenTech. The ST986, ST941, and ST2177 PDX models were derived at and studies run at South Texas Accelerated Research Therapeutics. MAXF-713 was derived at and studies run at Charles River Discovery. All animals were subcutaneously implanted with PDX models and began receiving estrogen supplementation in the drinking water from the date of tumor implant to the end of the study. The HBCx-19, HBCx-3, and HBCx-21 models were supplemented with 8.5 milligrams of 17β-estradiol to each liter of drinking water. The MAXF-713 model was supplemented with 10 milligrams of 17β-estradiol to each liter of drinking water. When tumors grew to 150–200 mm3, mice were randomized on the basis of tumor volume and administered the indicated treatments. At the end of study, tumors were harvested 4 hours post-last dose unless otherwise indicated.

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In vivo pharmacokinetic analyses[2]
Terminal plasma was collected via heart puncture and nonterminal plasma was collected via orbital bleeding. For all mice, blood samples were collected in potassium-EDTA–containing tubes and processed for pharmacokinetic analysis. Analysis of fulvestrant in mouse plasma samples was carried out using high-performance liquid chromatography on a Pursuit XRs 3 Diphenyl 100 × 2.0 mm column.

Absorption, Distribution and Excretion
With the recommended dosage of 345 mg once daily, elacestrant has a steady-state Cmax of 119 ng/mL and an AUC0-24h of 2440 ng⋅h/mL. The Cmax and AUC of elacestrant increase more than dose-proportional between 43 mg and 862 mg once daily (0.125 to 2.5 times the approved recommended dosage). By day 6, elacestrant reaches steady-state and has a 2-fold mean accumulation ratio based on AUC0-24h. The tmax of elacestrant goes from 1 to 4 hr, and its oral bioavailability is approximately 10%. Compared to a fasted state, the Cmax and AUC of elacestrant (345 mg) were 42% and 22% higher, respectively, when administered with a high-fat meal (800 to 1000 calories, 50% fat).
Elacestrant is mainly eliminated through feces and urine. Approximately 82% was recovered in feces (34% unchanged), and 7.5% was recovered in urine (< 1% unchanged) following a single radiolabeled oral dose of 345 mg.
Elacestrant has an apparent volume of distribution of 5800 L.
Elacestrant has an estimated clearance of 186 L/hr and a renal clearance of ≤ 0.14 L/hr.

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Metabolism / Metabolites
Elacestrant is metabolized in the liver, mainly by CYP3A4 and, to a lesser extent, by CYP2A6 and CYP2C9.

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Biological Half-Life
The elimination half-life of elacestrant is 30 to 50 hours.

Protein Binding
Elacestrant has a protein plasma binding higher than 99% and independent of concentration.

[1]. RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. Anticancer Drugs. 2015 Oct;26(9):948-56.

[2]. Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. Clin Cancer Res. 2017 Aug 15;23(16):4793-4804.

Pharmacodynamics
The exposure-response relationships and pharmacodynamics time course of elacestrant have not been fully characterized. At the approved recommended dose, the use of elacestrant does not lead to QTc interval increases higher than 20 msec. Hypercholesterolemia and hypertriglyceridemia have occurred in patients taking elacestrant, and administering this drug to pregnant women may cause fetal harm. Unlike other selective estrogen receptor modulators and degraders, elacestrant is capable of crossing the blood-brain barrier.

C₃₀H₃₈N₂O₂

458.63

458.293

C, 78.56; H, 8.35; N, 6.11; O, 6.98

722533-56-4

Elacestrant dihydrochloride;1349723-93-8;Elacestrant S enantiomer dihydrochloride;2309762-30-7;Elacestrant (S enantiomer);2309762-29-4

23642301

White to off-white solid powder

1.1±0.1 g/cm3

609.5±55.0 °C at 760 mmHg

322.4±31.5 °C

0.0±1.8 mmHg at 25°C

1.604

7.07

44.7

2

4

10

34

578

1

O(C([H])([H])[H])C1C([H])=C([H])C(=C(C=1[H])N(C([H])([H])C([H])([H])[H])C([H])([H])C1C([H])=C([H])C(C([H])([H])C([H])([H])N([H])C([H])([H])C([H])([H])[H])=C([H])C=1[H])[C@@]1([H])C([H])([H])C2C([H])=C([H])C(=C([H])C=2C([H])([H])C1([H])[H])O[H]

SIFNOOUKXBRGGB-AREMUKBSSA-N

InChI=1S/C30H38N2O2/c1-4-31-17-16-22-6-8-23(9-7-22)21-32(5-2)30-20-28(34-3)14-15-29(30)26-11-10-25-19-27(33)13-12-24(25)18-26/h6-9,12-15,19-20,26,31,33H,4-5,10-11,16-18,21H2,1-3H3/t26-/m1/s1

(6R)-6-[2-[ethyl-[[4-[2-(ethylamino)ethyl]phenyl]methyl]amino]-4-methoxyphenyl]-5,6,7,8-tetrahydronaphthalen-2-ol

RAD1901; RAD-1901; Elacestrant; 722533-56-4; ER-306323; elacestrantum; Elacestrant [INN]; Elacestrant [USAN];RAD 1901O; rserdu

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~160 mg/mL (~348.87 mM)

配方 1 中的溶解度: ≥ 4 mg/mL (8.72 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 40.0 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 4 mg/mL (8.72 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 40.0mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 4 mg/mL (8.72 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 40.0 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。