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LGK-974 Sale

(Synonyms: 2',3-二甲基-N-[5-(2-吡嗪基)-2-吡啶基]-[2,4'-联吡啶]-5-乙酰胺,WNT974) 目录号 : GC12392

A potent, bioavailable inhibitor of PORCN

LGK-974 Chemical Structure

Cas No.:1243244-14-5

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥1,040.00
现货
5mg
¥809.00
现货
50mg
¥4,778.00
现货
500mg
¥12,600.00
现货
1g
¥19,950.00
现货

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Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Cell experiment :

Cell lines

YAPC-STF cells, pancreatic cancer cells, HN30 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1 μM for 24-48 h

Applications

LGK974 specifically blocked the growth of pancreatic cancer cell lines harboring RNF43 mutation. LGK974 increased the cell surface level of Frizzled and decreased the mRNA levels of AXIN2 and RNF43 [1]. Moreover, LGK974 inhibited Wnt signaling in HN30 cells with an IC50 value of 0.3 nM [2].

Animal experiment :

Animal models

Mice bearing HPAF-II xenografts model, MMTV-Wnt1 tumor model

Dosage form

5 mg/kg; oral gavage (p.o.) twice daily (BID) for 14 -35 days; or 0.3, 1.0, and 3.0 mg/kg per day for 13 d.

Applications

Treatment of mice bearing HPAF-II xenografts with 5 mg/kg LGK974 resulted in significant inhibition of tumor growth. Furthermore, treatment of mice bearing Capan-2 xenografts with 5 mg/kg LGK974 achieved tumor stasis [1]. Moreover, LGK974 induced tumor regression by targeting Wnt signaling in a mechanistic MMTV-Wnt1 tumor model [2].

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Jiang, X., Hao, H. X., Growney, J. D., Woolfenden, S., Bottiglio, C., Ng, N., Lu, B., Hsieh, M. H., Bagdasarian, L., Meyer, R., Smith, T. R., Avello, M., Charlat, O., Xie, Y., Porter, J. A., Pan, S., Liu, J., McLaughlin, M. E. and Cong, F. (2013) Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A. 110, 12649-12654

2. Liu, J., Pan, S., Hsieh, M. H., Ng, N., Sun, F., Wang, T., Kasibhatla, S., Schuller, A. G., Li, A. G., Cheng, D., Li, J., Tompkins, C., Pferdekamper, A., Steffy, A., Cheng, J., Kowal, C., Phung, V., Guo, G., Wang, Y., Graham, M. P., Flynn, S., Brenner, J. C., Li, C., Villarroel, M. C., Schultz, P. G., Wu, X., McNamara, P., Sellers, W. R., Petruzzelli, L., Boral, A. L., Seidel, H. M., McLaughlin, M. E., Che, J., Carey, T. E., Vanasse, G. and Harris, J. L. (2013) Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 110, 20224-20229

产品描述

LGK-974 is a potent and specific small-molecule inhibitor of Porcupine (PORCN) with IC50 value of 1nM [1].

LGK-974 is discovered as a highly specific and potent PORCN inhibitor. Even 20μM LGK974 shows no significant cytotoxicity in cells. LGK-974 inhibits Wnt signaling in the Wnt co-culture assay with an IC50 of 0.4nM. It can block the PORCN-dependent Wnt secretion in a dose-dependent manner. In MMTV-Wnt1 tumor model, LGK-974 induces significant tumor regression through affecting the Wnt signaling events. It inhibits both AXIN2 expression and phospho-LRP6 (pLRP6) levels. It is proved that LGK974 promotes tumor regressions at doses that spare normal tissues. Additionally, LGK-974 potently reduces Wnt-dependent AXIN2 mRNA levels in HN30 cells with IC50 value of 0.3nM and it strongly attenuates HN30 colony formation, partly through inhibiting the β-catenin–dependent activities. Moreover, the anti-tumor efficacy has also been found in the mouse model of Wnt-dependent human HNSCC cell Line [1].

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.

Chemical Properties

Cas No. 1243244-14-5 SDF
别名 2',3-二甲基-N-[5-(2-吡嗪基)-2-吡啶基]-[2,4'-联吡啶]-5-乙酰胺,WNT974
化学名 2-[5-methyl-6-(2-methylpyridin-4-yl)pyridin-3-yl]-N-(5-pyrazin-2-ylpyridin-2-yl)acetamide
Canonical SMILES CC1=C(N=CC(=C1)CC(=O)NC2=NC=C(C=C2)C3=NC=CN=C3)C4=CC(=NC=C4)C
分子式 C23H20N6O 分子量 396.44
溶解度 ≥ 19.8mg/mL in DMSO 储存条件 Store at -20° C
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

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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
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