JW 74
目录号 : GC13978
An inhibitor of TNKS1/2
Cas No.:863405-60-1
Sample solution is provided at 25 µL, 10mM.
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IC50: 790 nM for canonical Wnt signaling
JW 74 is an inhibitor of the catalytic PARP domain of TNKS1/2.
Wnt/β-catenin, a major regulator of stem cell self-renewal and differentiation, is aberrantly activated in a several cancers, including osteosarcoma. Thus, attenuation of Wnt/β-catenin activity by tankyrase inhibitors is an appealing strategy in osteosarcoma treatment.
In vitro: Previous study found that JW74 at the molecular level induced stabilization of AXIN2, a key component of the β-catenin destruction complex, leading to reduced levels of nuclear β-catenin. In addition, JW74 could induce reduced cell growth in all tested cell lines, partially due to a delay in cell cycle progression and partially because of an induction of caspase-3-mediated apoptosis. Moreover, JW74 was able to induce the differentiation in U2OS cells and also enhance differentiation of OS cell lines that did not harbor a differentiation block [1].
In vivo: Previous animal study found that the dose of 150 mg/kg of JW74 in ApcMin model could reduce the small intestinal adenoma by 48% and was comparable with celecoxib or rofecoxib. Furthermore, it was noteworthy that JW74 became rapidly cleared from the blood stream due to its poor in vivo stability [2].
Clinical trial: Up to now, JW 74 is still in the preclinical development stage.
References:
1. E. W. Stratford, J. Daffinrud, E. Munthe, et al. The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines. Cancer Med. 3(1), 36-46 (2014).
2. Waaler J et al. Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth. Cancer Res. 2011 Jan 1;71(1):197-205.
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Cell experiment: |
The cell lines U2OS, SaOS-2, and KPD are cultured in RPMI-1640. Two to three thousand cells attached overnight in 96-well plates are treated with culturing medium containing 0.1% DMSO (control) or JW74 (10-0.1 μM). Proliferation rates based on cell confluence are determined by live cell imaging. Cellular viability is also determined by MTS assay. Expression of the proliferation marker Ki-67 is performed by staining cells with PE-mouse anti-human Ki-67 and by analyzing the expression by flow cytometry[2]. |
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Animal experiment: |
Mice[1]40 female C.B-Igh-1b/IcrTac-Prkdcscid mice are injected subcutaneously (s.c.) at the right posterior flank with 107 SW480 cells diluted in 100 μL PBS. Injections are initiated when tumor formation is visible in 50 % of the animals (7 days). Mice are randomized and divided into three treatment groups: JW74 150 mg/kg, JW74 300 mg/kg and vehicle control, 1 % Tween 80. Daily intra peritoneal (i.p.) injections (200 μL) with two day injection intermissions after every fifth injection day are performed until the experiment end (29 days). At the termination day, 24 hours after the last injection, blood is collected after cardiac puncture and tumors are dissected and weighed. The compound concentration in tumors and blood are determined using on-line and off-line Solid Phase Extraction-Capillary Liquid Chromatography (SPE-CapLC) instrumentation coupled to a Time of Flight (TOF) mass spectrometer. A Zorbax SB C18 5 μm 150×0.3 mm column is used for separation, and a Knauer K-2600 UV detector is used as a complimentary detector. |
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References: [1]. Waaler J, et al. Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth. Cancer Res. 2011 Jan 1;71(1):197-205. |
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| Cas No. | 863405-60-1 | SDF | |
| 化学名 | 4-[4-(4-methoxyphenyl)-5-[[[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]thio]-4H-1,2,4-triazol-3-yl]-pyridine | ||
| Canonical SMILES | CC(C=C1)=CC=C1C2=NOC(CSC3=NN=C(C4=CC=NC=C4)N3C5=CC=C(OC)C=C5)=N2 | ||
| 分子式 | C24H20N6O2S | 分子量 | 456.5 |
| 溶解度 | ≤20mg/ml in DMSO;20mg/ml in dimethyl formamide | 储存条件 | Store at -20°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 | 2.1906 mL | 10.9529 mL | 21.9058 mL |
| 5 mM | 0.4381 mL | 2.1906 mL | 4.3812 mL |
| 10 mM | 0.2191 mL | 1.0953 mL | 2.1906 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet