# LGK974

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**LGK974** (**WNT974**) is an experimental drug which acts as an inhibitor of the [porcupine O-acyltransferase](/source/PORCN) enzyme, which plays an important part in the growth of certain types of cancer, especially [colorectal cancer](/source/Colorectal_cancer), [pancreatic cancer](/source/Pancreatic_cancer), [hepatocellular carcinoma](/source/Hepatocellular_carcinoma) and head and neck cancers. It is in early stage [clinical trials](/source/Clinical_trial) for a number of cancer types.[1][2][3]

LGK974 has recently shown promise in preclinical models of the ultra-rare disease [sclerosteosis](/source/Sclerosteosis), providing an alternative to invasive surgeries commonly required to the management of pathologies.[4]

## References

1. Zhang LS, Lum L (January 2018). "Chemical Modulation of WNT Signaling in Cancer". *Progress in Molecular Biology and Translational Science*. **153**: 245–269. [doi:10.1016/bs.pmbts.2017.11.008](https://doi.org/10.1016/bs.pmbts.2017.11.008). ISBN 978-0-12-811429-2. [PMID 29389519](https://pubmed.ncbi.nlm.nih.gov/29389519)

1. Shah K, Panchal S, Patel B (May 2021). "Porcupine inhibitors: Novel and emerging anti-cancer therapeutics targeting the Wnt signaling pathway". *Pharmacological Research*. **167**. [doi:10.1016/j.phrs.2021.105532](https://doi.org/10.1016/j.phrs.2021.105532). [PMID 33677106](https://pubmed.ncbi.nlm.nih.gov/33677106)

1. Goswami VG, Patel BD (November 2021). "Recent updates on Wnt signaling modulators: a patent review (2014-2020)". *Expert Opinion on Therapeutic Patents*. **31** (11): 1009–1043. [doi:10.1080/13543776.2021.1940138](https://doi.org/10.1080/13543776.2021.1940138). [PMID 34128760](https://pubmed.ncbi.nlm.nih.gov/34128760)

1. Dreyer TJ, Keen JA, Wells LM, Hopkinson M, Orriss IR, Holdsworth G, Pitsillides AA, Roberts SJ (April 2025). "Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies". *Bone Research*. **13** (1). [doi:10.1038/s41413-025-00406-3](https://doi.org/10.1038/s41413-025-00406-3). [PMC 11973224](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973224). [PMID 40189599](https://pubmed.ncbi.nlm.nih.gov/40189599)

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