Tankyrase Inhibitors 22 is a potent, selective, and orally bioavailable inhibitor of tankyrase (IC50: 0.1nM).

Tankyrase inhibitors 22 is an optimization of the previous hit compound inhibitor 8 with improved potency and selectivity. It has excellent effects in both tankyrase assay and cellular assay (IC50: 0.1nM and 3.7nM, respectively). In addition, it is found to be a dual binder with both the nicotinamide pocket and the induced pocket of the enzymes [1].

In the in vivo studies in rodents, tankyrase inhibitors 22 is found to potently inhibit TNKS2 autoparsylation (IC50: 4.1nM). It also causes stabilization and accumulation of axin protein in SW480 cells (EC50: 3.9nM). In DLD-1 cells with truncated APC, the inhibitor inhibits the STF reporter transcription (IC50: 0.6nM) suggesting its downstream inhibitory activity on Wnt-associated transcription [1].