Definition

An inhibitor of activin A receptor type 1 (activin receptor-like kinase 2; ALK2; ALK-2; ACVR1; ACTR-I), with potential anti-anemic and ossification suppressive activities. Upon administration, ALK2 inhibitor INCB000928 targets, binds to and inhibits the activity of ALK-2. This prevents ALK2-mediated signaling and ALK2-mediated excessive bone morphogenetic protein (BMP) signaling. This may suppress heterotopic ossification (HO). As ALK-2 enhances the secretion of hepcidin, a peptide liver hormone and a key modulator of iron homeostasis, INCB000928 is able to decrease hepcidin expression in the liver, thereby increasing and restoring plasma iron levels, enhancing erythropoiesis, and correcting anemia of chronic disease (ACD). ALK2, a serine/threonine receptor kinase and type I cell surface receptor for BMPs, is constitutively activated due to activating mutations in inflammatory conditions, various types of cancer, and in fibrodysplasia ossificans progressiva (FOP). Elevated serum hepcidin levels enhance storage of iron, reduce iron availability and causes iron deficiency anemia.