切换导航

AZD2461

现货
Catalog No.
A4164
PARP抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,190.00
现货
5mg
¥ 750.00
现货
10mg
¥ 1,200.00
现货
50mg
¥ 3,800.00
Ship with 10-15 days
100mg
¥ 5,400.00
Ship with 10-15 days

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

AZD2461 is a novel PARP inhibitor with IC50 value of 5nM [1].
Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes involving mainly DNA repair and programmed cell death [1].
In SKBR-3 line and MCF-7 line, AZD2461 was cytotoxic and reduced numbers of viable cells in a concentration- and time-dependent manner. Also, through inhibiting PARP-1, AZD2461 increased MCF-7 cells and SKBR-3 cells in the G2 phase at the expense of proportions in the S- phase, respectively [2].
In order to investigate whether long-term dosing of AZD2461 would be capable of causing eradication or chronic suppression of KB1P tumors, which acquired Pgp-mediated resistance, we tested the response of KB1P tumors to the novel AZD2461. Both AZD2461 and olaparib completely inhibited the PARP activity for several hours, and 24 hours after treatment the amount of PAR returned to baseline levels. These data show that AZD2461 is a novel PARPi with potential to bypass Pgp-mediated resistance to olaparib. With short-term treatment, AZD2461 induces loss of 53BP1 expression in mice with KB1P tumors. Long-term AZD2461 treatment is well tolerated and doubled the median relapse-free survival [1].
Reference:
[1]. Jaspers JE, Kersbergen A, Boon U, et al. Loss of 53BP1 Causes PARP Inhibitor Resistance in Brca1-Mutated Mouse Mammary Tumors. Cancer Discov, 2013, 3(1): 68-81.
[2]. Węsierska GJ, Heinzl S. Interactions Between Ataxia Telangiectasia Mutated Kinase Inhibition, Poly(ADP-ribose) Polymerase-1 Inhibition and BRCA1 Status in Breast Cancer Cells. J Cancer Prev. 2014, 19(2): 125–136.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt395.43
Cas No.1174043-16-3
FormulaC22H22FN3O3
Solubility≥16.35 mg/mL in DMSO, ≥45.2 mg/mL in EtOH with ultrasonic, <2.37 mg/mL in H2O
Chemical Name4-[[4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one
SDFDownload SDF
Canonical SMILESCOC1CCN(CC1)C(=O)C2=C(C=CC(=C2)CC3=NNC(=O)C4=CC=CC=C43)F
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

人MCF-7和SKBr-3乳腺癌细胞

溶解方法

该化合物在DMSO中的溶解度>16.35mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

5-50 μM, 48和72h

应用

在人MCF-7和SKBr-3乳腺癌细胞中,AZD2461具有细胞毒性并以浓度和时间依赖的方式减少活细胞数量。 AZD2461(10μM,48小时)对PARP-1的抑制增加了G2期MCF-7细胞比例并减少S期细胞。

动物实验[2]:

动物模型

具有KB1P肿瘤的小鼠

剂量

100 mg/kg,口服, 连续28天或连续100天

应用

在具有KB1P肿瘤的小鼠中,AZD2461完全抑制PARP活性数小时,并且在治疗后24小时PARP的量回到基线水平。AZD2461对Pgp的亲和力比olaparib低。连续28天用AZD2461处理的小鼠显示出增加的存活率。当用AZD2461连续100天处理时,在移植了3个KB1P肿瘤片段的9只小鼠中有8只在治疗开始后的300天内未发展为难治性肿瘤。 长期AZD2461治疗耐受性良好,中位无复发生存期从64天增加到132天。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Wsierska GJ, Heinzl S. Interactions Between Ataxia Telangiectasia Mutated Kinase Inhibition, Poly(ADP-ribose) Polymerase-1 Inhibition and BRCA1 Status in Breast Cancer Cells. J Cancer Prev. 2014, 19(2): 125–136.

[2]. Jaspers JE, Kersbergen A, Boon U, et al. Loss of 53BP1 Causes PARP Inhibitor Resistance in Brca1-Mutated Mouse Mammary Tumors. Cancer Discov, 2013, 3(1): 68-81.

生物活性

Description AZD2461是一种新的PARP抑制剂。
靶点 PARP          
IC50            

质量控制

质量控制和MSDS

批次:

化学结构

AZD2461