LGK974

LGK974
Identifiers
	IUPAC name 2-[5-methyl-6-(2-methylpyridin-4-yl)pyridin-3-yl]-N-(5-pyrazin-2-ylpyridin-2-yl)acetamide;
CAS Number	210826-47-4;
PubChem CID	46926973;
IUPHAR/BPS	11167;
DrugBank	DB12561;
ChemSpider	30507712;
UNII	U27F40013Q;
ChEBI	CHEBI:78030;
ChEMBL	ChEMBL3188386;
PDB ligand	O50 (PDBe, RCSB PDB);
Chemical and physical data
Formula	C23H20N6O
Molar mass	396.454 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=CN=C1C2=CC(=NC=C2)C)CC(=O)NC3=NC=C(C=C3)C4=NC=CN=C4;
	InChI InChI=1S/C23H20N6O/c1-15-9-17(12-28-23(15)18-5-6-25-16(2)10-18)11-22(30)29-21-4-3-19(13-27-21)20-14-24-7-8-26-20/h3-10,12-14H,11H2,1-2H3,(H,27,29,30); Key:XXYGTCZJJLTAGH-UHFFFAOYSA-N;

LGK974 (WNT974) is an experimental drug which acts as an inhibitor of the PORCN or Porcupine protein. It inhibits the production of β-Catenin which plays an important part in the growth of certain types of cancer, especially colorectal cancer, pancreatic cancer, hepatocellular carcinoma and head and neck cancers. It is in early stage clinical trials for a number of cancer types.^[1]^[2]^[3]

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

References

^ 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. ISBN 978-0-12-811429-2. PMID 29389519.
^ Shah K, Panchal S, Patel B (May 2021). "Porcupine inhibitors: Novel and emerging anti-cancer therapeutics targeting the Wnt signaling pathway". Pharmacological Research. 167: 105532. doi:10.1016/j.phrs.2021.105532. PMID 33677106.
^ 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. PMID 34128760.
^ Dreyer TJ, Keen JA, Wells LM, Hopkinson M, Orriss IR, Holdsworth G, et al. (April 2025). "Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies". Bone Research. 13 (1): 44. doi:10.1038/s41413-025-00406-3. PMC 11973224. PMID 40189599.{{cite journal}}: CS1 maint: overridden setting (link)

[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. ISBN 978-0-12-811429-2. PMID 29389519.

[2] Shah K, Panchal S, Patel B (May 2021). "Porcupine inhibitors: Novel and emerging anti-cancer therapeutics targeting the Wnt signaling pathway". Pharmacological Research. 167: 105532. doi:10.1016/j.phrs.2021.105532. PMID 33677106.

[3] 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. PMID 34128760.

[4] Dreyer TJ, Keen JA, Wells LM, Hopkinson M, Orriss IR, Holdsworth G, et al. (April 2025). "Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies". Bone Research. 13 (1): 44. doi:10.1038/s41413-025-00406-3. PMC 11973224. PMID 40189599.{{cite journal}}: CS1 maint: overridden setting (link)

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