| Identification | Back Directory | [Name]
LGK-974 | [CAS]
1243244-14-5 | [Synonyms]
CS-1102
LGK-974
WNT-974
NVP-LGK974
LGK974 (WNT974)
LGK974; LGK-974
LGK-974 USP/EP/BP
LGK974(NVP-LGK974)
LGK974; LGK 974; NVP-LGK974
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]-
2-(2',3-Dimethyl-2,4'-bipyridin-5-yl)-N-[5-(2-pyrazinyl)-2-pyridi nyl]acetamide
2-(2',3-diMethyl-[2,4'-bipyridin]-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetaMide
2-[5-Methyl-6-(2-methyl-4-pyridyl)-3-pyridyl]-N-(5-pyrazin-2-yl-2-pyridyl)acetamide
2-(2',3-Dimethyl-[2,4'-bipyridin]-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide hydrochloride
LGK-974 2',3-Dimethyl-N-[5-(2-pyrazinyl)-2-pyridinyl]-[2,4'-bipyridine]-5-acetamide | [Molecular Formula]
C23H20N6O | [MDL Number]
MFCD27501026 | [MOL File]
1243244-14-5.mol | [Molecular Weight]
396.44 |
| Chemical Properties | Back Directory | [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) | [form ]
Solid | [pka]
12.24±0.70(Predicted) | [color ]
White to Off-White |
| Hazard Information | Back Directory | [Description]
Porcupine (PORCN) is a membrane bound O-acyltransferase that mediates palmitoylation of Wnt family proteins.1 This step is required for secretion and biologic activity of Wnt proteins, which have roles in embryonic development and cancer.1,2 LGK974 is a potent and specific small molecule inhibitor of PORCN (IC50 = 0.4 nM).3 It greatly reduces Wnt secretion without decreasing its synthesis and without increasing cytotoxicity.3 LGK974 is orally bioavailable in mice and induces tumor regression in mouse breast tumors produced by mammary tumor virus-driven Wnt1 signaling.3 It also blocks carcinogenesis in other Wnt-related tumors at doses that have limited impact on stem cell renewal.3,4,5 | [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]
LGK974, a drug that targets Porcupine, a Wnt-specific acyltransferase. LGK974 potently inhibits Wnt signaling, has strong efficacy in rodent tumor models, and is well-tolerated. Toxicology studies are performed on nontumor bearing rats at 3 and 20 mg/kg. At the efficacious dose of 3 mg/kg per day for 14 d, LGK974 is well-tolerated without abnormal histopathological findings in Wnt-dependent tissues, including the intestine, stomach, and skin. When rats are administrated a very high dose of 20 mg/kg per day for 14 d, loss of intestinal epithelium is observed, consistent with the concept that Wnt is required for intestinal tissue homeostasis[1]. | [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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