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

Porcupine (PORCN) is a membrane bound O-acyltransferase that mediates palmitoylation of Wnt family proteins. This step is required for secretion and biologic activity of Wnt proteins, which have roles in embryonic development and cancer. LGK974 is a potent and specific small molecule inhibitor of PORCN (IC50 = 0.4 nM). It greatly reduces Wnt secretion without decreasing its synthesis and without increasing cytotoxicity. LGK974 is orally bioavailable in mice and induces tumor regression in mouse breast tumors produced by mammary tumor virus-driven Wnt1 signaling. It also blocks carcinogenesis in other Wnt-related tumors at doses that have limited impact on stem cell renewal.

Uses

LGK 974 is a potent and specific small molecule Porcupine (PORCN) inhibitor.

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.