LGK974, known as WNT974, represents a highly specific and orally bioavailable inhibitor of Porcupine (PORCN), a key enzyme involved in the post-translational modification of Wnt proteins, with an impressive IC50 of 0.1 nM[1].
体内研究
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].
体外研究
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].
作用机制
LGK interacts with PORCN to inhibit its acyltransferase activity.
LGK974 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
293T
Function Assay
IC50 of 1 nM to compete off [3H]-GNF-1331 in a dose-dependent manner
24277854
293T
Function Assay
IC50 of 0.4 nM to inhibits Wnt signaling in the aforementioned Wnt coculture assay
24277854
Capan-2
1 μM
Growth Inhibition Assay
inhibits the growth of pancreatic cancer cell lines with RNF43 mutation
23847203
HPAF-II
1 μM
Growth Inhibition Assay
inhibits the growth of pancreatic cancer cell lines with RNF43 mutation
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