CGX1321 (CGX-1321) is a nove potent and specific inhibitor of porcupine (PORCN) that inhibits Wnt pathway, block secretion of WNT proteins with IC50 of 1 nM.
CGX1321 displayed >500 times selective for Porcupine over the most related target enzyme, hedgehog acyltransferase
CGX1321 increased Ki67+ and phosphohistone H3 (PH3+) cardiomyocytes in culture, up-regulated cell cycle regulating genes such as Ccnb1 and Ccne1, did not alter YAP protein phosphorylation and nuclear translocation in cardiomyocytes.
CGX1321 administration blocked the secretion of Wnt proteins, and inhibited both canonical and non-canonical Wnt signaling pathways in MI injury mice.
CGX1321 improved cardiac function, reduced myocardial infarct size, and fibrosis of post-MI hearts.
CGX1321 significantly increased newly formed cardiomyocytes in infarct border zone of post-MI hearts, evidenced by the increased EdU+ cardiomyocytes.