JW 55
(Synonyms: Tankyrase 1/2 Inhibitor IV) 目录号 : GC12869
A TNKS1/2 inhibitor
Cas No.:664993-53-7
Sample solution is provided at 25 µL, 10mM.
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IC50: 1.9 μM (TNK S1); 0.83 μM (TNK S2)
Increased nuclear accumulation of β-catenin, a mediator of canonical Wnt signaling, is found in numerous tumors and is frequently associated with tumor progression and metastasis. Inhibition of Wnt/b-catenin signaling therefore is an attractive strategy for anticancer drugs.
In vitro: In a previous study, the authors identified a novel small molecule inhibitor of the β-catenin signaling pathway, JW55, that functions via inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2), regulators of the b-catenin destruction complex. Inhibition of TNKS1/2 poly(ADP-ribosyl)ation activity by JW55 led to stabilization of AXIN2, a member of the b-catenin destruction complex, followed by increased degradation of b-catenin. In a dose-dependent manner, JW55 inhibited canonical Wnt signaling in colon carcinoma cells that contained mutations in either the APC (adenomatous polyposis coli) locus or in an allele of b-catenin [1].
In vivo: JW55 was reported to reduce XWnt8-induced axis duplication in Xenopus embryos and tamoxifen-induced polyposis formation in conditional APC mutant mice. These findings provide a novel chemotype for targeting canonical Wnt/b-catenin signaling through inhibiting the PARP domain of TNKS1/2 [1].
Clinical trial: JW55 is currently in the preclinical development and no clinical trial is ongoing.
Reference:
[1] Waaler J, Machon O, Tumova L, Dinh H, Korinek V, Wilson SR, Paulsen JE, Pedersen NM, Eide TJ, Machonova O, Gradl D, Voronkov A, von Kries JP, Krauss S. A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice. Cancer Res. 2012;72(11):2822-32.
Cell experiment: | A total of 1,000 SW480 or RKO cells are seeded in 96-well plates. The day after, the cell culture medium is exchanged to solutions that contained 0.1% DMSO or 10 μM JW55 for RKO cells and 0.1% DMSO or 10, 5, or 1 μM JW55 for SW480 cells. All samples consist of a minimum of 6 replicates. The plate is incubated in an IncuCyte inside a cell culture incubator. Images are captured every second hour to monitor proliferation[1]. |
Animal experiment: | Mice[1] Seven 12-week old female ApcCKO/CKO/Lgr5-CreERT2 mice are injected intraperitonally with 25 mg/kg of Tamoxifen diluted in an ethanol and corn oil (ratio 1:4). The mice are randomized into 2 groups and treated with either JW55 (100 mg/kg) or vehicle (DMSO). Daily per oral applications started the day after and continued for 3 weeks. The mouse body weight is measured twice a week. The mice are sacrificed and the intestines are dissected, washed in PBS, and fixed in formaldehyde [10% solution (v/v) in PBS]. The small intestines are stained using 1% methylene blue prepared in 10% paraformalaldehyde (PFA)/PBS solution. Small ileum Swiss-rolls are embedded in paraffin sectioned and stained with hematoxylin and eosin. Fixed colons are embedded in paraffin, sectioned and stained with an anti-β-catenin antibody. The number and size of the intestinal lesions are quantified by the Ellipse program. |
References: [1]. Waaler J, et al. A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice. Cancer Res. 2012 Jun 1;72(11):2822-32. | |
| Cas No. | 664993-53-7 | SDF | |
| 别名 | Tankyrase 1/2 Inhibitor IV | ||
| 化学名 | N-[4-[[4-(4-methoxyphenyl)oxan-4-yl]methylcarbamoyl]phenyl]furan-2-carboxamide | ||
| Canonical SMILES | COC1=CC=C(C=C1)C2(CCOCC2)CNC(=O)C3=CC=C(C=C3)NC(=O)C4=CC=CO4 | ||
| 分子式 | C25H26N2O5 | 分子量 | 434.48 |
| 溶解度 | ≥ 19.25mg/mL in DMSO, ≥ 3.53 mg/mL in EtOH with ultrasonic | 储存条件 | Store at 4°C |
| 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3016 mL | 11.508 mL | 23.016 mL |
| 5 mM | 0.4603 mL | 2.3016 mL | 4.6032 mL |
| 10 mM | 0.2302 mL | 1.1508 mL | 2.3016 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet