AZD9496
(Synonyms: (E)-3-[3,5-二氟-4-[(1R,3R)-2-(2-氟-2-甲基丙基)-3-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-B]吲哚-1-基]苯基]丙烯酸) 目录号 : GC14405
A SERD
Cas No.:1639042-08-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Effect of AZD9496, Fulvestrant, and Tamoxifen 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 Fulvestrant for the time indicated. Data shown is representative of two independent experiments[1]. |
Animal experiment: | 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. |
References: [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. | |
IC50: 0.82, 0.14 and 0.28 nM for ERα binding, ERα downregulation, ERα antagonism, respectively
AZD9496 is an orally active estrogen receptor inhibitor.
Estrogen receptors (ERs) are a group of proteins presented inside and on cells, and they are receptors that are activated by the hormoneestrogen. ERs are found to be over-expressed in about 70% of breast cancer cases, referred to as "ER-positive".
In vitro: AZD9496 was identified as a nonsteroidal small-molecule inhibitor of ERα, which was a potent and selective antagonist and downregulator of ERα. In addition, AZD9496 could bind and downregulate clinically relevant ESR1 mutants [1].
In vivo: Animal study reported that significant tumor growth inhibition was observed as low as 0.5 mg/kg dose of AZD9496 in the estrogen-dependent MCF-7 xenograft model, and such effect was accompanied by a dose-dependent decrease in PR protein levels, providing potent antagonist activity. In addition, the combination of AZD9496 with PI3K pathway and CDK4/6 inhibitors resulted in further growth-inhibitory effects when compared with monotherapy alone. Furthermore, the tumor regression was also observed in a long-term estrogen-deprived breast model, in which significant ERα protein downregulation was found [1].
Clinical trial: AZD9496 is currently being evaluated in a phase I clinical trial to assess the PK and safety of different forms and formulations [2].
References:
[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] https://clinicaltrials. gov/ct2/show/NCT02780713 term=AZD9496&rank=2
| Cas No. | 1639042-08-2 | SDF | |
| 别名 | (E)-3-[3,5-二氟-4-[(1R,3R)-2-(2-氟-2-甲基丙基)-3-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-B]吲哚-1-基]苯基]丙烯酸 | ||
| 化学名 | (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 | ||
| Canonical SMILES | O=C(O)/C=C/C1=CC(F)=C([C@H]2N(CC(C)(F)C)[C@H](C)CC3=C2NC4=CC=CC=C34)C(F)=C1 | ||
| 分子式 | C25H25F3N2O2 | 分子量 | 442.47 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,Ethanol:PBS (pH 7.2) (1:6): 0.14 mg/mL | 储存条件 | 4°C, protect from light, stored under nitrogen |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.26 mL | 11.3002 mL | 22.6004 mL |
| 5 mM | 0.452 mL | 2.26 mL | 4.5201 mL |
| 10 mM | 0.226 mL | 1.13 mL | 2.26 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。