RK-582 (RK582) is a highly selective, potent and orally efficacious tankyrase inhibitor with IC50 of 39.1 and 36.2 nM for TNKS1/TNKS2, respectively.
RK-582 shows high potency comparable with that of RK-287107 and G007-LK, displays no significant effect (>200-fold selectivity) against human PARP family member enzymes PARP1, PARP2 (poly ADPribosylation), and PARP10 (mono ADP-ribosylation).
RK-582 exhibits a high potency for the inhibition of TCF reporter activities at IC50 values of HEK293 (0.3 nM) and DLD-1 cells (3.1 nM).
RK-582 exhibited potent GI50 (35 nM), high sensitivity and sigmoid dependency achieving complete growth inhibition at 10 uM on CRC cells via MTT assays.
RK-582 induced AXIN2 accumulation and downregulation of β-catenin.
RK-582 (10 or 20 mg/kg, twice daily, oral or i.p.) exhibited a markedly robust tumor growth inhibition in a COLO-320DM mouse xenograft model.
