切换导航

Tankyrase Inhibitors (TNKS) 49

现货
Catalog No.
A8601
端锚聚合酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,900.00
现货
5mg
¥ 2,000.00
现货
10mg
¥ 3,500.00
现货
50mg
¥ 9,500.00
现货
100mg
¥ 15,000.00
Ship with 10-15 days

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

Tankyrase Inhibitors (TNKS) 49 is a potent, selective and orally bioavailable inhibitor of tankyrase with IC50 value of 0.1nM [1].

Tankyrase 1 and tankyrase 2 are members of PARP family. They can use NAD+ as substrates to transfer ADP-ribose polymers onto tagert proteins. The tankyrase are found to bind to PARSylate axin proteins which are the negative regulator of Wnt pathway. It makes tankyrase to be targets in treatment for adenomatous polyposis coli. Tankyrase inhibitors 49 is an optimization of the previous hit compound inhibitor 8 with improved potency and selectivity. It has excellent effects in both tankyrase assay and cellular assay (total β-catenin degradation assay in SW480 cells) with IC50 values of 0.1nM and 1.9nM, respectively. In addition, it is found to be a dual binder with both the nicotinamide pocket and the induced pocket of the enzymes [1].

In the in vivo studies in rodents, tankyrase inhibitors 49 is found to potently inhibit TNKS2 autoparsylation with IC50 value of 7.6nM. It also causes stabilization and accumulation of axin protein in SW480 cells with EC50 value of 4nM. In DLD-1 cells with truncated APC, the inhibitor inhibits the STF reporter transcription with IC50 value of 0.3nM suggesting its downstream inhibitory activity on Wnt-associated transcription [1].

References:
[1] Hua Z, Bregman H, Buchanan J L, et al. Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors. Journal of medicinal chemistry, 2013, 56(24): 10003-10015.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt448.54
FormulaC24H24N4O3S
SynonymsTNKS 49;TNKS49;TNKS-49
Solubility≥22.45mg/mL in DMSO
Chemical NameN-((1r,4r)-4-(4-cyanophenoxy)cyclohexyl)-3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanamide
SDFDownload SDF
Canonical SMILESO=C1NC(SCCC(N[C@H]2CC[C@H](OC3=CC=C(C#N)C=C3)CC2)=O)=NC4=CC=CC=C41
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

SW480-TBC细胞系

制备方法

该化合物在DMSO中的溶解度大于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

24 h,IC50 = 1.9 nM

实验结果

Tankyrase Inhibitors (TNKS) 49是一种苯氧基化合物,具有良好的酶效价和细胞效价,在SW480-TBC细胞中IC50值为1.9 nM。在TNKS2自动糖化测定和两种另外的功能细胞测定中,该化合物显示出优异的效力。

动物实验: [1]

动物模型

Athymic裸鼠

给药剂量

10 and 50 mg/kg,每天一次,口服

实验结果

在小鼠肿瘤药效学(PD)模型中评价Tankyrase Inhibitors (TNKS) 49对Wnt途径的特异性药理活性。对携带人DLD-1肿瘤的小鼠(n = 4)每天一次口服给药(10和50 mg/kg)3天,在第3天最后一次给药后24小时,两种化合物均具有统计学显著的、剂量依赖性的axin2积累(2.7-3.5倍) 和STF抑制(51-58%)。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Hua Z, Bregman H, Buchanan J L, et al. Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors[J]. Journal of medicinal chemistry, 2013, 56(24): 10003-10015.

质量控制

化学结构

Tankyrase Inhibitors (TNKS) 49