Tankyrase Inhibitors 49 is an effective, selective, and orally bioavailable inhibitor of tankyrase (IC50: 0.1nM).

Tankyrase inhibitors 49 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 1.9nM, 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 49 is found to potently inhibit TNKS2 autoparsylation ( IC50: 7.6nM). It also causes stabilization and accumulation of axin protein in SW480 cells (EC50: 4nM). In DLD-1 cells with truncated APC, the inhibitor inhibits the STF reporter transcription ( IC50: 0.3nM) suggesting its downstream inhibitory activity on Wnt-associated transcription [1].