JW55

JW 55 is a potent and selective β-catenin signaling pathway inhibitor, which functions via inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2). JW 55 decreases auto-PARsylation of TNKS1/2 in vitro with IC50s of 1.9 μM and 830 nM respectively.

Research Areas >> Cancer

TNKS2:0.83 μM (IC50)

TNKS1:1.9 μM (IC50)

JW 55 (JW55) is a potent and selective inhibitor of the canonical Wnt pathway. Wnt3a-induced HEK293 cells containing a transiently transfected ST-Luc (SuperTop-luciferase) reporter show inhibition by JW55 with an IC50 value of 470 nM. JW55 is effective in the range of 1 to 5 μM in SW480 cells and 0.01 to 5 μM in HCT-15 cells. JW55 is effective in the range of 1 to 5 μM in SW480 cells and 0.01 to 5 μM in HCT-15 cells[1].

JW 55 (100 mg/kg, orally) reduces tumor development in conditional Apc knockout mice. JW55 reduces XWnt8-induced axis duplication inXenopus embryos and Tamoxifen-induced polyposis formation in conditional APC mutant mice[1].

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].

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.

[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.

Talazoparib | XAV-939 | MK-4827(Niraparib) | Veliparib (ABT-888) | Rucaparib (AG-014699) phosphate | PJ34 HCl | Pamiparib | Rucaparib camsylate | E-7449 | AZD2461 | G007-LK | Iniparib (BSI-201) | NMS-P118 | A-966492 | AG14361