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MedKoo CAT#: 205851
CAS#: 1243244-14-5 (free base)
Description: LGK974, also known as WNT974, is a selective and orally bioavailable porcupine (PORCN) inhibitor under development for the treatment of cancers that are driven by the Wnt pathway in a Wnt ligand-dependent manner. WNT974 binds to and inhibits PORCN in the endoplasmic reticulum (ER), which blocks post-translational acylation of Wnt ligands and inhibits their secretion. This prevents the activation of Wnt ligands, interferes with Wnt-mediated signaling, and inhibits cell growth in Wnt-driven tumors. Porcupine, a membrane-bound O-acyltransferase (MBOAT), is required for the palmitoylation of Wnt ligands, and plays a key role in Wnt ligand secretion and activity. Wnt signaling is dysregulated in a variety of cancers.
MedKoo Cat#: 205851
Name: LGK974
CAS#: 1243244-14-5 (free base)
Chemical Formula: C23H20N6O
Exact Mass: 396.16986
Molecular Weight: 396.44
Elemental Analysis: C, 69.68; H, 5.08; N, 21.20; O, 4.04
Related CAS #: 2375595-49-4 (2HCl) 1243244-14-5 (free base)
Synonym: LGK974; LGK-974; LGK 974; WNT974; WNT 974; WNT-974
IUPAC/Chemical Name: 2-(2',3-dimethyl-[2,4'-bipyridin]-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide
InChi Key: XXYGTCZJJLTAGH-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(NC1=NC=C(C2=NC=CN=C2)C=C1)CC3=CN=C(C4=CC(C)=NC=C4)C(C)=C3
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. doi: 10.1073/pnas.1314239110. Epub 2013 Nov 25. PubMed PMID: 24277854; PubMed Central PMCID: PMC3864356.
2: Jiang X, Hao HX, Growney JD, Woolfenden S, Bottiglio C, Ng N, Lu B, Hsieh MH, Bagdasarian L, Meyer R, Smith TR, Avello M, Charlat O, Xie Y, Porter JA, Pan S, Liu J, McLaughlin ME, Cong F. Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12649-54. doi: 10.1073/pnas.1307218110. Epub 2013 Jul 11. PubMed PMID: 23847203; PubMed Central PMCID: PMC3732970.
