LGK-974 (Synonyms: PORCN Inhibitor IV)

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 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