LGK974 is a potent and orally active Wnt pathway inhibitor with an IC50<1 nM in the Wnt signaling assay . It inhibits acylation of Wnt proteins by Porcupine (Porcn). LGK974 specifically blocks the proliferation of pancreatic cancer cells that have up-regulated Wnt signaling caused by carrying inactive mutations in a Ubiquitin E3 ligase, RNF43 .
LGK974 robustly suppressed Wnt signaling in vivo resulting in tumor regression in a murine breast cancer model driven by MMTV-Wnt1, and showed excellent efficacy in xenograft models of head and neck squamous cell carcinoma and pancreatic cancer . Currently LGK974 is in the Phase I study to treat patients with different types of Wnt signaling-driven cancers .
|Solubility:||Up to 100 mM in DMSO|
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder or DMSO solution at -20oC desiccated.
|1.||Shifeng Pan. Discovery of LGK974: A selective Porcupine inhibitor targeting Wnt signaling in cancer. AACR Annual Meeting 2013.|
|2.||Jiang X, et al. Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proc Natl Acad Sci USA. 2013; 110(31):12649-54. Pubmed ID: 23847203|
|3.||Liu J, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 2013; 110(50):20224-9 Pubmed ID: 24277854|