LGK-974 Chemical Properties

Melting point:

176 - 180°C

Boiling point:

650.9±55.0 °C(Predicted)

Density 

1.268±0.06 g/cm3(Predicted)

storage temp. 

Refrigerator

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

12.24±0.70(Predicted)

form 

Solid

color 

White to Off-White

InChI

InChI=1S/C23H20N6O/c1-15-9-17(12-28-23(15)18-5-6-25-16(2)10-18)11-22(30)29-21-4-3-19(13-27-21)20-14-24-7-8-26-20/h3-10,12-14H,11H2,1-2H3,(H,27,29,30)

InChIKey

XXYGTCZJJLTAGH-UHFFFAOYSA-N

SMILES

C1(C2C=CN=C(C)C=2)=NC=C(CC(NC2=NC=C(C3=NC=CN=C3)C=C2)=O)C=C1C

Safety Information

HS Code 

2933399990

LGK-974 Usage And Synthesis

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.

Definition

ChEBI: LGK974 is a carboxamide, the structure of which is that of acetamide substituted on carbon by a 2',3-dimethyl-2,4'-bipyridin-5-yl group and on nitrogen by a 5-(pyrazin-2-yl)pyridin-2-yl group. It is a highly potent, selective and orally bioavailable Porcupine inhibitor (a Wnt signalling inhibitor). It has a role as a Wnt signalling inhibitor. It is a member of bipyridines, a member of pyrazines, a member of pyridines and a secondary carboxamide. It is functionally related to an acetamide.

in vivo

target

PORCN

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.

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