JW 55 (Synonyms: Tankyrase 1/2 Inhibitor IV) |
| Catalog No.GC12869 |
A TNKS1/2 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| Sinónimos | Tankyrase 1/2 Inhibitor IV | ||
| Chemical Name | 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 | ||
| Formula | C25H26N2O5 | M.Wt | 434.48 |
| Solubility | ≥ 19.25mg/mL in DMSO, ≥ 3.53 mg/mL in EtOH with ultrasonic | Storage | Store at 4°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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