In rodent tumor models, LGK974 demonstrates potent anti-tumor activity and tolerability. Toxicological assessments in non-tumor-bearing rats at doses of 3 and 20 mg/kg indicate that LGK974 is well-tolerated at the efficacious dose of 3 mg/kg per day over 14 days, without histopathological changes in Wnt-dependent tissues. However, a high dose of 20 mg/kg per day for the same duration results in loss of intestinal epithelium, highlighting the essential role of Wnt signaling in maintaining intestinal tissue homeostasis^[1].

LGK974 also displaces [³H]-GNF-1331 with an IC50 of 1 nM in a PORCN radioligand binding assay and significantly reduces AXIN2 mRNA levels, a Wnt target gene, in HN30 cells with an IC50 of 0.3 nM^[1].