Irigenin is a is a lead compound, and mediates its anti-metastatic effect by specifically and selectively blocking α9β1 and α4β1 integrins binding sites on C-C loop of Extra Domain A (EDA). Irigenin shows anti-cancer properties. It sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells[1].
Irigenin specifically targets α9β1 and α4β1 integrin binding sites on Extra Domain A (EDA) comprising LEU46, PHE47, PRO48, GLU58, LEU59 and GLN60 in its C-C loop. Irigenin binds to the C-C loop of EDA, thereby blocking its interaction with integrins on the cell surface and thus abrogating subsequent Epithelial-Mesenchymal transition[1].
[1]. Amin A, et al. Irigenin, a novel lead from Western Himalayan chemiome inhibits Fibronectin-Extra Domain A induced metastasis in Lung cancer cells. Sci Rep. 2016 Nov 16;6:37151. [2]. Xu Y, et al. Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells. Biochem Biophys Res Commun. 2018 Feb 12;496(3):998-1005.