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AZD8931 (Sapitinib)

现货
Catalog No.
A8375
ErbB抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,030.00
现货
5mg
¥ 990.00
现货
10mg
¥ 1,840.00
现货
50mg
¥ 5,990.00
现货

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Background

Description:
IC50: AZD8931 showed equipotent, reversible inhibition of EGFR (IC50, 4 nmol/L), erbB2 (IC50, 3 nmol/L), and erbB3 (IC50, 4 nmol/L) phosphorylation in cells
The erbB receptor family is composed of four related receptor tyrosine kinases [epidermal growth factor receptor (EGFR, erbB1), erbB2 (human epidermal growth factor receptor 2, HER2), erbB3 (HER3), and erbB4 (HER4)]. AZD8931 is a novel small-molecule equipotent inhibitor of EGFR, HER2, and HER3 signaling.
In vitro: In a previous in vitro study, the authors investigated the antitumor activity of AZD8931 alone or in combination with paclitaxel using preclinical models of EGFR-overexpressed and HER2 non-amplified IBC cells. Results showed that AZD8931 significantly suppressed cell growth of IBC cells and induced apoptosis of human IBC cells in vitro [2].
In vivo: In a previous study, the authors investigated the antitumor activity of AZD8931 alone or in combination with paclitaxel IBC cells were orthotopically transplanted into the mammary fat pads of immunodeficient mice. AZD8931 was given by daily oral gavage at doses of 25 mg/kg, 5 days/week for 4 weeks. Paclitaxel was subcutaneously injected twice weekly. Results showed that AZD8931 monotherapy inhibited xenograft growth and the combination of paclitaxel + AZD8931 was demonstrably more effective than paclitaxel or AZD8931 alone treatment at delaying tumor growth in vivo in orthotopic IBC models. These results suggest that AZD8931 may provide a novel therapeutic strategy for the treatment of IBC patients with HER2 non-amplified tumors [2].
Clinical trial: A phase I/II clinical trial is conducted to determine if AZD8931 can improve the efficacy of standard chemotherapy for the treatment of advanced breast cancer. This study will be conducted in 2 parts: the first part (phase I) will determine a dose of AZD8931 that can be safely administered with paclitaxel chemotherapy. The second part (phase II) will determine the efficacy and safety of AZD8931 in combination with paclitaxel chemotherapy in breast cancer (https://clinicaltrials.gov/ct2/show/NCT00900627).
References:
[1] Hickinson DM, Klinowska T, Speake G, Vincent J, Trigwell C, Anderton J, Beck S, Marshall G, Davenport S, Callis R, Mills E, Grosios K, Smith P, Barlaam B, Wilkinson RW, Ogilvie D. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor, ERBB2 (HER2), and ERBB3: a unique agent for simultaneous ERBB receptor blockade in cancer. Clin Cancer Res. 2010;16(4):1159-69.
[2] Mu Z, Klinowska T, Dong X, Foster E, Womack C, Fernandez SV, Cristofanilli M. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor (EGFR), HER2, and HER3: preclinical activity in HER2 non-amplified inflammatory breast cancer models. J Exp Clin Cancer Res. doi: 10.1186/1756-9966-33-47.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt473.93
Cas No.848942-61-0
FormulaC23H25ClFN5O3
Solubility≥23.7 mg/mL in DMSO, ≥57.8 mg/mL in EtOH with gentle warming, <2.49 mg/mL in H2O
Chemical Name2-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-N-methylacetamide
SDFDownload SDF
Canonical SMILESCNC(=O)CN1CCC(CC1)OC2=C(C=C3C(=C2)C(=NC=N3)NC4=C(C(=CC=C4)Cl)F)OC
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

NSCLC和SCCHN细胞株,KB细胞,MCF-7细胞

溶解方法

该化合物在DMSO中的溶解度大于23.7 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

96 h

应用

在KB细胞中,AZD8931抑制配体刺激的EGFR磷酸化。AZD8931还抑制亲本MCF-7细胞和MCF-7cl24细胞中erbB2和erbB3介导的信号转导。在NSCLC和头颈鳞状细胞癌细胞中,AZD8931明显抑制肿瘤细胞生长。

动物实验[1]:

动物模型

BT474c (乳腺癌)、Calu-3 (非小细胞肺癌)、LoVo (结直肠癌)、FaDu (头颈鳞状细胞癌)和 PC-9 (非小细胞肺癌) 肿瘤异种移植小鼠模型

给药剂量

口服,6.25-50 mg/kg,每天两次

应用

AZD8931抑制EGFR敏感和erbB2敏感性人肿瘤异种移植模型的生长。在人肿瘤异种移植模型中,AZD8931导致增殖和凋亡标志物的药效学变化。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Mu Z, Klinowska T, Dong X, et al. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor (EGFR), HER2, and HER3: preclinical activity in HER2 non-amplified inflammatory breast cancer models[J]. Journal of Experimental & Clinical Cancer Research, 2014, 33(1): 47.

生物活性

描述 AZD8931 是一种可逆的ATP 竞争性EGFR、ErbB2 和ErbB3抑制剂,IC50 值分别为4 nM、3 nM和4 nM。
靶点 ErbB2 EGFR ErbB3      
IC50 3 nM 4 nM 4 nM      

质量控制

化学结构

AZD8931 (Sapitinib)