企业QQ
官方微信
LGK974 is a potent and orally active Wnt pathway inhibitor with an IC50<1 nM in the Wnt signaling assay [1]. 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 [2].
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 [3]. Currently LGK974 is in the Phase I study to treat patients with different types of Wnt signaling-driven cancers [4].
Technical information:
| Chemical Formula: | C23H20N6O | |
| CAS #: | 1243244-14-5 | |
| Molecular Weight: | 396.44 | |
| Purity: | > 98% | |
| Appearance: | White | |
| Chemical Name: | 2-(2,3-dimethyl-[2,4-bipyridin]-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | NVP-LGK974, LGK974 |
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.
Reference:
| 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 |
| 4. | http://clinicaltrials.gov/show/NCT01351103 |