WNT-974

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效且特异性的小分子豪猪 (PORCN) 抑制剂，在 PORCN 放射性配体结合测定中 IC50 为 1 nM。

A potent and specific small-molecule Porcupine (PORCN) inhibitor with IC50 of 1 nM in the PORCN radioligand binding assay; potently inhibits Wnt signaling with IC50 of 0.4 nM, with no major cytotoxicity; reduces Wnt-dependent LRP6 phosphorylation and the expression of Wnt target genes, such as AXIN2; is potent and efficacious in multiple tumor models at well-tolerated doses in vivo.Colon Cancer Phase 2 Clinical(In Vitro):LGK974 effectively displaces [3H]-GNF-1331 with an IC50 of 1 nM in the PORCN radioligand binding assay. LGK974 potently reduces Wnt-dependent AXIN2 mRNA levels in HN30 cells with an IC50 of 0.3 nM.(In Vivo):LGK974, a drug that targets Porcupine, a Wnt-specific acyltransferase. LGK974 potently inhibits Wnt signaling, has strong efficacy in rodent tumor models, and is well-tolerated. Toxicology studies are performed on nontumor bearing rats at 3 and 20 mg/kg. At the efficacious dose of 3 mg/kg per day for 14 d, LGK974 is well-tolerated without abnormal histopathological findings in Wnt-dependent tissues, including the intestine, stomach, and skin. When rats are administrated a very high dose of 20 mg/kg per day for 14 d, loss of intestinal epithelium is observed, consistent with the concept that Wnt is required for intestinal tissue homeostasis.

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LGK-974 | LGK974 | LGK 974 | WNT 974 | WNT974

Wnt/Notch/Hedgehog

Porcupine

Porcn

Cancer

Colon Cancer

1243244-14-5

396.4445

C23H20N6O

>98% (HPLC)

DMSO: ≥ 32 mg/mL

O=C(NC1=NC=C(C2=NC=CN=C2)C=C1)CC3=CN=C(C4=CC(C)=NC=C4)C(C)=C3

[2,4'-Bipyridine]-5-acetamide, 2',3-dimethyl-N-[5-(2-pyrazinyl)-2-pyridinyl]-

(-20℃)

With Ice Pack

≥ 2 years