Tankyrase-IN-2 is an inhibitor of the tankyrases TNKS1 and TNKS2 (IC50s = 7 and 9.2 nM, respectively).1 It is selective for TNKS1 and TNKS2 over a panel of 10 additional poly(ADP-ribose) polymerases (PARPs; IC50s = 710->10,000 nM for the human enzymes). Tankyrase-IN-2 increases accumulation of Axin2 and TNKS, indicating inhibition of TNKS-mediated auto-PARsylation, in DLD-1 colorectal cancer cells with EC50 values of 319 and 320 nM, respectively. It also increases tumor Axin2 and TNKS accumulation, as well as decreases tumor levels of active β-catenin, in a DLD-1 mouse xenograft model when administered at doses of 10, 30, and 90 mg/kg.
1.Buchstaller, H.-P., Anlauf, U., Dorsch, D., et al.Discovery and optimization of 2-arylquinazolin-4-ones into a potent and selective tankyrase inhibitor modulating Wnt pathway activityJ. Med. Chem.62(17)7897-7909(2019)