LGK-974
(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
Cas No.:1243244-14-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment : | |
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Cell lines |
YAPC-STF cells, pancreatic cancer cells, HN30 cells |
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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. |
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Reacting condition |
1 μM for 24-48 h |
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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 : | |
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Animal models |
Mice bearing HPAF-II xenografts model, MMTV-Wnt1 tumor model |
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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. |
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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]. |
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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. |
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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 |
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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.
| 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。 |
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| 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。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。