Biological Activity:

NVP-TNKS656 is a highly potent, selective and oral bioavailable tankyrase inhibitor with IC50 of 6 nM for TNKS2. It has 300-fold selectivity against PARP1 and PARP2. In MMTV-Wnt1 tumor models, NVP-TNKS656 was dosed to mice orally to stabilize Axin1 protein and reduce the Wnt/beta-catenin target gene Axin2 mRNA level by 70-80%. In colorectal cancer PDX models, NVP-TNKS656 reduces nuclear β-catenin, reverts such resistance, and represses tumor growth.

How to Use:

In vitro: NVP-TNKS656 was used at 10 µM in vitro and cellular assays.
In vivo: In MMTV-Wnt1 tumor bearing athymic nude mice, NVP-TNKS656 was dosed to mice orally at 100-350 mg/Kg once per day to stabilize Axin1 protein and reduce the Wnt/beta-catenin target gene Axin2 mRNA level by 70-80%. In colorectal cancer PDX models, NVP-TNKS656 reduces nuclear β-catenin, reverts such resistance, and represses tumor growth.

Reference:

• 1. Shultz MD, et al. Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor. (2013) J Med Chem. 56(16):6495-511. 
• 2. Arqués O, et al. Tankyrase Inhibition Blocks Wnt/β-Catenin Pathway and Reverts Resistance to PI3K and AKT Inhibitors in the Treatment of Colorectal Cancer. (2016) Clin Cancer Res. 22(3):644-56.