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Colorectal tumors, in particular, often show dysregulated WNT/β-catenin signalling. G007-LK may be a candidate for use in preclinical trials to determine the efficacy of this drug in preventing growth of WNT dependent tumors. Doses of the tankyrase inhibitor G007-LK shown to be sufficient to inhibit tumor growth are well tolerated by mice within the time frames investigated. Lineage tracing from LGR5+ intestinal stem cells was reduced upon G007-LK treatment, without altering the main morphological characteristics of the intestine. Moreover, mice treated with G007-LK did not experience weight loss, suggesting that the absorptive capacity of the intestine was not negatively impacted.

Medicilon Preclinical Research LCC performed the pharmacokinetic studies.

Reference:

Jens Henrik Norum, et al. The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology. Biol Res. 2018 Jan 9;51(1):3. doi: 10.1186/s40659-017-0151-6.