WNT974

WNT974 (also known as LGK974) is an orally bioavailable small molecule inhibitor of the enzyme Porcupine (PORCN), a membrane-bound O-acyltransferase (MBOAT) essential for the post-translational palmitoylation and secretion of Wnt ligands. By inhibiting PORCN, WNT974 prevents the release of Wnt proteins, thereby suppressing Wnt-mediated signaling pathways which are frequently dysregulated in various cancers. Developed by Novartis, WNT974 is being investigated in collaboration with the University of Michigan Rogel Cancer Center specifically for the treatment of metastatic head and neck squamous cell carcinoma (HNSCC). Clinical research focuses on patients with Notch receptor mutations (particularly NOTCH1 loss-of-function), as preclinical data suggests these tumors are uniquely sensitive to Wnt pathway inhibition.

Other names

Porcupine inhibitor WNT974