Luspatercept

Specification

• Cat#: THP-0398
• Product Name: Luspatercept
• Description: Luspatercept is an erythroid maturation agent used to treat anemia secondary to beta thalassemia, myelodysplastic syndromes, and neoplasms.
• Species: 1373715-00-4
• Molecular Weight: Luspatercept; luspatercept-aamt
• Source: The average apparent volume of distribution is 7.1 L.
• Purity: Not Available
• Biological Activity: The total apparent clearance of luspatercept is 0.44 L/day.
• Form: As luspatercept is a fusion protein, it is expected to undergo catabolism into amino acids by general protein degradation processes.
• Concentration: AQK7UBA1LS
• Endotoxin Level: Repeat-dose toxicity studies in juvenile rats showed an increase in the development of hematologic malignancies at doses of 10 mg/kg, a dose approximately 8-fold higher than the maximum recommended human dose (MRHD). Fertility studies in rats observed effects on female (but not male) fertility at doses approximately 7-fold higher than the MRHD.

Pharmaceutical Information

• Targets: Beta thalassemia is a genetic red blood cell disorder caused by mutations in the β-globin gene - these mutations cause oxidative stress and premature apoptosis of erythroblasts, thereby leading to ineffective erythropoesis. The transforming growth factor beta (TGF-β) superfamily of endogenous ligands (including activins, growth differentiation factors, and bone morphogenetic proteins) are involved in the inhibition of erythroid differentiation via activation of the Smad2/3 subfamily of intracellular effectors. Luspatercept is a fusion protein comprising a modified extracellular domain of activin receptor type IIB (a target for many TGF-β ligands) fused to the FC domain of human IgG1. Luspatercept ameliorates ineffective erythropoiesis in patients with beta thalassemia by acting as a "ligand trap" for various members of the TGF-β superfamily, preventing their downstream signalling and subsequent inhibition of late-stage erythroid maturation. The specific members of the TGF-β superfamily targeted by luspatercept are currently unknown, though growth differentiation factor 11 (GDF11) has been experimentally excluded as a potential target.