1243244-14-5

Basic information

• Product Name: LGK-974
• Synonyms: LGK-974;2-(2',3-diMethyl-[2,4'-bipyridin]-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetaMide;2',3-Dimethyl-N-[5-(2-pyrazinyl)-2-pyridinyl]-[2,4'-bipyridine]-5-acetamide;[2,4'-Bipyridine]-5-acetamide, 2',3-dimethyl-N-[5-(2-pyrazinyl)-2-pyridinyl]-;NVP-LGK974;LGK-974 2',3-Dimethyl-N-[5-(2-pyrazinyl)-2-pyridinyl]-[2,4'-bipyridine]-5-acetamide;LGK974(NVP-LGK974);2-[5-Methyl-6-(2-methyl-4-pyridyl)-3-pyridyl]-N-(5-pyrazin-2-yl-2-pyridyl)acetamide
• CAS NO: 1243244-14-5
• Molecular Formula: C₂₃H₂₀N₆O
• Molecular Weight: 396.4445
• Product Categories: Inhibitors
• Mol File: 1243244-14-5.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 650.9±55.0 °C(Predicted)
• Appearance: /
• Density: 1.268±0.06 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 12.24±0.70(Predicted)
• CAS DataBase Reference: LGK-974(CAS DataBase Reference)
• NIST Chemistry Reference: LGK-974(1243244-14-5)
• EPA Substance Registry System: LGK-974(1243244-14-5)

Safety Data

• Hazardous Substances Data: 1243244-14-5(Hazardous Substances Data)

Usage

Description

LGK-974 is a potent and specific small molecule inhibitor of Porcupine (PORCN), a membrane-bound O-acyltransferase that plays a crucial role in the palmitoylation of Wnt family proteins, which is essential for their secretion and biological activity. This inhibition is significant in the context of embryonic development and cancer.

Uses

Used in Pharmaceutical Industry:
LGK-974 is used as an anticancer agent targeting the Wnt signaling pathway, which is implicated in various cancers. By inhibiting PORCN, LGK-974 greatly reduces Wnt secretion without decreasing its synthesis and without increasing cytotoxicity, making it a promising candidate for cancer treatment.
Used in Cancer Research:
LGK-974 is used as a research tool to study the role of Wnt signaling in cancer development and progression. Its ability to block Wnt secretion and induce tumor regression in mouse breast tumors driven by mammary tumor virus Wnt1 signaling provides valuable insights into the mechanisms of Wnt-related carcinogenesis.
Used in Drug Development:
LGK-974 is used in the development of novel therapeutics for Wnt-driven cancers. Its oral bioavailability in mice and its ability to block carcinogenesis in other Wnt-related tumors at doses with limited impact on stem cell renewal make it a potential candidate for further drug development and clinical trials.

references

[1] liu j, pan s, hsieh mh, ng n, sun f, wang t, kasibhatla s, schuller ag, li ag, cheng d, li j, tompkins c, pferdekamper a, steffy a, cheng j, kowal c, phung v, guo g, wang y, graham mp, flynn s, brenner jc, li c, villarroel mc, schultz pg, wu x, mcnamara p, sellers wr, petruzzelli l, boral al, seidel hm, mclaughlin me, che j, carey te, vanasse g, harris jl. targeting wnt-driven cancer through the inhibition of porcupine by lgk974. proc natl acad sci u s a. 2013 dec 10;110(50):20224-9.

Upstream product

• 29241-60-9 5-bromo-2-chloro-3-methylpyridine 

Relevant articles and documents

Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors

Blockade of aberrant Wnt signaling is an attractive therapeutic approach in multiple cancers. We developed and performed a cellular high-throughput screen for inhibitors of Wnt secretion and pathway activation. A lead structure (GNF-1331) was identified from the screen. Further studies identified the molecular target of GNF-1331 as Porcupine, a membrane bound O-acyl transferase. Structure-activity relationship studies led to the discovery of a novel series of potent and selective Porcupine inhibitors. Compound 19, GNF-6231, demonstrated excellent pathway inhibition and induced robust antitumor efficacy in a mouse MMTV-WNT1 xenograft tumor model.