RAP-536

RAP-536 is a murine surrogate of luspatercept (ACE-536), a first-in-class erythroid maturation agent. It is a recombinant fusion protein consisting of a modified extracellular domain of the murine activin receptor type IIB (ActRIIB) linked to the Fc portion of murine IgG. RAP-536 acts as a ligand trap, sequestering members of the transforming growth factor-beta (TGF-β) superfamily, including growth differentiation factor 11 (GDF-11) and activin B, which are negative regulators of late-stage erythropoiesis. By inhibiting these ligands, RAP-536 reduces Smad2/3 signaling, thereby promoting the maturation of late-stage erythroblasts and increasing red blood cell production. It is extensively used in preclinical research to evaluate the therapeutic potential of ActRIIB-based ligand traps in murine models of anemia, beta-thalassemia, and sickle cell disease (SCD). In SCD models, RAP-536 has been shown to ameliorate anemia and reduce vaso-occlusive crises by improving red blood cell deformability and reducing reactive oxygen species.

Other names

murine luspatercept analogmurine ActRIIB-IgG analog