G007-LK

G007-LK is a potent inhibitor of TNKS1 and TNKS2, with IC ₅₀ s of 46 nM and 25 nM, respectively, and a cellular IC ₅₀ of 50 nM. G007-LK shows no inhibition of PARP1 at doses up to 20 μM, and has a high CYP3A4 inhibition IC ₅₀ value (>25 μM). G007-LK (0-20 μM) dose-dependently inhibits hepatocellular carcinoma (HCC) cell growth. G007-LK also downregulates the levels of YAP by upregulating AMOTL1 and AMOTL2 in HCC cell lines. In addition, G007-LK (0-20 μM) synergizes with MEK and AKT inhibitors to suppress HCC cell proliferation.

G007-LK displays great pharmacokinetic profile in ICR mice. G007-LK (100 mg/kg chow, p.o.) significantly reduces lineage tracing from LGR5 ⁺ intestinal stem cells in mice. G007-LK (100 mg/kg chow, p.o.) specifically targets LGR5 ⁺ WNT-dependent intestinal stem cells in Lgr5-EGFP-CreERT2;R26R-tdTomato mice. G007-LK (10, 50 mg/kg, p.o.) also suppressses canonical WNT signalling. Furthermore, G007-LK (100, 1000 mg/kg chow, p.o) shows no effect on the alteration of duodenal morphology.