AZD9496

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

AZD9496  纯度: 99.28%

AZD9496 是有效,选择性的雌激素受体 (ERα) 拮抗剂,IC50 为 0.28 nM。AZD9496 是一种口服有效的选择性雌激素受体降解剂 (SERD)

AZD9496

AZD9496 Chemical Structure

CAS No. : 1639042-08-2

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ¥1265 In-stock
5 mg ¥1320 In-stock
10 mg ¥2280 In-stock
25 mg ¥4560 In-stock
50 mg ¥6840 In-stock
100 mg ¥10200 In-stock
200 mg   询价  
500 mg   询价  

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AZD9496 相关产品

相关化合物库:

  • Clinical Compound Library Plus
  • Bioactive Compound Library Plus
  • Anti-Cancer Compound Library
  • Clinical Compound Library
  • Orally Active Compound Library
  • Chemical Probe Library
  • Anti-Breast Cancer Compound Library

生物活性

AZD9496 is a potent and selective estrogen receptor (ERα) antagonist with an IC50 of 0.28 nM. AZD9496 is an orally bioavailable selective oestrogen receptor degrader (SERD).

IC50 & Target

IC50: 0.28 nM (ERα antagonism), 0.14 nM (ERα downregulation), 0.82 nM (ERα binding)[1]

体外研究
(In Vitro)

The potency of AZD9496 with IC50 of 0.82 nM, 0.14 nM, and 0.28 nM in ERα binding, downregulation, and antagonism, respectively. AZD9496 significantly inhibits MCF-7 cell growth with EC50 of 0.04 nM[1]. Selectivity of AZD9496 over other tested nuclear hormone receptors is high: androgen receptor (AR), IC50=30 μM; glucocorticoid receptor (GR), IC50=9.2 μM; progesterone receptor (PR), IC50=0.54 μM[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.

体内研究
(In Vivo)

Significant tumor growth inhibition is observed as low as 0.5 mg/kg dose in the estrogen-dependent MCF-7 xenograft model, where this effect is accompanied by a dose-dependent decrease in PR protein levels, demonstrating potent antagonist activity. Combining AZD9496 with PI3K pathway and CDK4/6 inhibitors lead to further growth-inhibitory effects compared with monotherapy alone. AZD9496, given once daily orally at 5 and 25 mg/kg produced statistically significant increases in uterine weight compared with the ICI 182780 control (P<0.001) but significantly lower than ICI 47699 (P=0.001)[1]. AZD9496 is also tested in a long-term estrogen deprived model (LTED), using the HCC-1428 LTED cell line that grows in the absence of estrogen and is thought to best represent a model of aromatase inhibition. AZD9496 shows significant activity, with a dose of 5 mg/kg giving tumor regressions in this model[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.

Clinical Trial

分子量

442.47

Formula

C25H25F3N2O2

CAS 号

1639042-08-2

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

溶解性数据
In Vitro: 

DMSO : ≥ 104.5 mg/mL (236.17 mM)

H2O : < 0.1 mg/mL (insoluble)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.2600 mL 11.3002 mL 22.6004 mL
5 mM 0.4520 mL 2.2600 mL 4.5201 mL
10 mM 0.2260 mL 1.1300 mL 2.2600 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (5.65 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.65 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: 2.5 mg/mL (5.65 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.5 mg/mL (5.65 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Weir HM, et al. AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. Cancer Res. 2016 Jun 1;76(11):3307-18.

    [2]. De Savi C, et al. Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist. J Med Chem. 2015 Oct 22;58(20):8128-40.

Cell Assay
[1]

Effect of AZD9496, ICI 182780, and ICI 47699 on ERα peptide turnover in MCF-7 cells. Cells are grown in steroid-free conditions in SILAC media containing 13C615N4 L-arginine to label ERα peptide as “heavy” (blue line) and then switched to grow in media containing unlabeled L-arginine to label newly synthesized protein as “normal” (red line) with 0.1% DMSO, 300 nM Tamoxife, 100 nM AZD9496, or 100 nM ICI 182780 for the time indicated. Data shown is representative of two independent experiments[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.

Animal Administration
[1]

Mice[1]
In vivo efficacy of AZD9496 in MCF-7 xenograft model. MCF-7 xenografts, grown in male SCID mice, are dosed daily with either PEG/captisol (vehicle) or AZD9496 (0.02, 0.1, 0.5, 10, and 50 mg/kg, p.o., q.d.). Tumor growth is measured by caliper at regular intervals and mean tumor volumes plotted for each dosed group.

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.

参考文献
  • [1]. Weir HM, et al. AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. Cancer Res. 2016 Jun 1;76(11):3307-18.

    [2]. De Savi C, et al. Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist. J Med Chem. 2015 Oct 22;58(20):8128-40.

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