G007-LK

G007-LK is an inhibitor of the tankyrases TNKS1 and TNKS2 (IC₅₀s = 46 and 25 nM, respectively).¹ It is selective for TNKS1 and TNKS2 over a panel of 90 kinases, 16 phosphatases, and 73 G protein-coupled receptors (GPCRs) when used at a concentration of 10 µM. G007-LK inhibits colony formation of COLO 320 DM and SW403 colorectal cancer cell lines when used at a concentration of 200 µM, as well as human hepatocellular carcinoma (HCC) cells in a dose-dependent manner.^2,3 It increases expression of intestinal differentiation markers in COLO 320 DM and HCT15 cells when used at a concentration of 100 nM. G007-LK inhibits Wnt3A-induced signaling in human HEK293 and mouse 10T1/2 cells.² G007-LK (20 mg/kg, i.p., twice daily) also inhibits tumor growth in COLO 320 DM and SW403 mouse xenograft models, however, it leads to intestinal toxicity when administered at a dose of 30 mg/kg twice daily, leading to moribundity and death.

WARNING This product is not for human or veterinary use.

1. Voronkov, A., Holsworth, D.D., Waaler, J., et al. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase ½ inhibitor. J. Med. Chem. 56(7), 3012-3023 (2013).

2. Lau, T., Chan, E., Callow, M., et al. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res. 73(10), 3132-3144 (2013).

3. Jia, J., Quao, Y., Pilo, M.G., et al. Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade. PLoS One 12(9), e0184068 (2017).