Zilurgisertib fumarate (INB-000928 fumarate) is a potent and selective inhibitor of Activin Receptor-Like Kinase 2 (ALK2/ACVR1). It significantly inhibits ALK2 kinase activity (IC50 = 15 nM) and downregulates BMP-6-induced SMAD1/5 phosphorylation (IC50 = 63 nM). By blocking ALK2-mediated signaling, Zilurgisertib suppresses the production of hepcidin in hepatocytes (IC50 = 20 nM), thereby modulating iron metabolism. In preclinical studies, Zilurgisertib demonstrates the potential to improve anemia in cancer-induced models by effectively increasing hemoglobin levels.

ALK2:15 nM, Smad1/5:63 nM, Hepcidin production:20 nM