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LGK-974

现货
Catalog No.
B2307
PORCN抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,400.00
Ship with 10-15 days
5mg
¥ 1,100.00
Ship with 10-15 days
50mg
¥ 6,400.00
Ship with 10-15 days

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Background

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.

文献引用

1. Shen X, Pan B, et al. "Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway." J Biomed Sci. 2017 May 10;24(1):29. PMID:28490365

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt396.44
Cas No.1243244-14-5
FormulaC23H20N6O
Solubility≥19.8mg/mL in DMSO
Chemical Name2-[5-methyl-6-(2-methylpyridin-4-yl)pyridin-3-yl]-N-(5-pyrazin-2-ylpyridin-2-yl)acetamide
SDFDownload SDF
Canonical SMILESCC1=C(N=CC(=C1)CC(=O)NC2=NC=C(C=C2)C3=NC=CN=C3)C4=CC(=NC=C4)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 :

细胞系

YAPC-STF细胞,胰腺癌细胞,HN30细胞

溶解方法

该化合物在DMSO中的溶解度 > 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

1 μM,24-48小时

应用

LGK974特异性阻断携带RNF43突变的胰腺癌细胞系的生长。LGK974增加卷曲蛋白的细胞表面水平,并降低AXIN2和RNF43的mRNA水平 [1]。此外,LGK974抑制HN30细胞中的Wnt信号,IC50值为0.3 nM [2]。

动物实验 :

动物模型

携带HPAF-II的小鼠异种移植模型,MMTV-Wnt1肿瘤模型

剂量

5 mg/kg; 口服管饲(p.o.),每日两次(BID),14-35天; 或0.3、1.0和3.0 mg/kg每天一次,持续13天。

应用

用5 mg/kg LGK974处理携带HPAF-II异种移植物的小鼠导致肿瘤生长的显著抑制。此外,用5 mg/kg LGK974处理携带Capan-2异种移植物的小鼠实现肿瘤生长停滞 [1]。此外,LGK974在机械性MMTV-Wnt1肿瘤模型中通过靶向Wnt信号传导,诱导肿瘤消退 [2]。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

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

生物活性

描述 LGK-974是一种有效的和特异性的PORCN抑制剂。
靶点 PORCN          
IC50            

质量控制

化学结构

LGK-974

相关生物数据

LGK-974