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Purity: ≥98%
LGK-974 (formerly known as WNT-974; LGK-974 and NVP-LGK974) is a novel potent, orally bioavailable and specific/selective PORCN (Porcupine) inhibitor with potential anticancer activity. It inhibits Wnt signaling with an IC50 of 0.4 nM in TM3 cells. LGK974 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. LGK-974 is being investigated for the treatment of cancers driven by the Wnt pathway in a Wnt ligand-dependent manner.
| ln Vitro |
LGK974 efficiently displaces [3H]-GNF-1331 in PORCN radioligand binding assays, with an IC50 of 1 nM. In HN30 cells, LGK974 efficiently lowers Wnt-dependent AXIN2 mRNA levels with an IC50 of 0.3 nM[1].
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| ln Vivo |
The medication LGK974, which targets the Wnt-specific acyltransferase Porcupine. Strongly suppressing Wnt signaling, well-tolerated, and highly effective in rodent tumor models is LGK974. Rats without tumors were used in toxicology tests at doses of 3 and 20 mg/kg. LGK974 was well tolerated at an effective dose of 3 mg/kg per day for 14 days, and no aberrant histopathological abnormalities were observed in tissues that depend on Wnt, such as the stomach, intestines, or skin. Rats given very high dosages (20 mg/kg per day) for 14 days showed loss of intestinal epithelial cells, which is consistent with the idea that Wnt is necessary for intestinal tissue homeostasis [1].
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| References |
[1]. Liu J, et al. 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.
[2]. Tammela T, et al. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature. 2017 May 18;545(7654):355-359 |
| Molecular Formula |
C23H20N6O
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| Molecular Weight |
396.44
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| CAS # |
1243244-14-5
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| Related CAS # |
2375595-49-4 (2HCl);1243244-14-5;
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| SMILES |
O=C(NC1=NC=C(C2=NC=CN=C2)C=C1)CC3=CN=C(C4=CC(C)=NC=C4)C(C)=C3
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| Chemical Name |
2-(2',3-dimethyl-[2,4'-bipyridin]-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide
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| Synonyms |
NVP-LGK974; NVPLGK974; NVP LGK974; LGK974; LGK-974; LGK 974; WNT974; WNT 974; WNT-974
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL | |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL | |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 LGK974 inhibits tumor growth ofRNF43-mutant pancreatic tumors in vivo.Proc Natl Acad Sci U S A.2013Jul 30;110(31):12649-54. |
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 LGK974 specifically inhibits the growth of pancreatic cancer cell lines harboringRNF43mutation.Proc Natl Acad Sci U S A.2013Jul 30;110(31):12649-54. |
 Characterization ofRNF43mutations in pancreatic cancer.Proc Natl Acad Sci U S A.2013Jul 30;110(31):12649-54. |
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