Transforming growth factor-beta superfamily ligands binding activin receptor type IIB (ACVR2B ligands)

The TGF-β superfamily ligands that bind to the activin receptor type IIB (ACVR2B) include a group of potent signaling proteins such as myostatin (GDF-8), activin A, activin B, and GDF-11. These ligands are central regulators of tissue growth and differentiation, specifically acting as negative regulators of skeletal muscle mass and inhibitors of late-stage erythropoiesis (UniProt P54763, P33316). In various diseases, the overactivation of these ligands leads to pathological muscle wasting (sarcopenia and cachexia) and impaired red blood cell maturation (PMID: 28435100). Therapeutic strategies targeting these ligands primarily utilize ligand traps, which are recombinant fusion proteins consisting of the extracellular domain of ACVR2B (or its relative ACVR2A) fused to an IgG Fc fragment. These traps, such as luspatercept, sequester circulating ligands to prevent them from binding to and activating the cell-surface ACVR2B receptor, thereby promoting muscle growth and stimulating erythropoiesis (PMID: 32075877). Clinical applications of these therapies include the treatment of anemia in beta-thalassemia and myelodysplastic syndromes, as well as investigations into pulmonary arterial hypertension and muscle-wasting disorders (FDA Reblozyl Label).

Other names

MyostatinGrowth differentiation factor 8GDF-8Growth differentiation factor 11GDF-11Activin AActivin BInhibin beta AInhibin beta BBone morphogenetic protein 10BMP-10

Ligand sequestration via decoy receptors (ligand traps) or monoclonal antibodies to prevent activation of the activin receptor type IIB signaling pathway.