Repositioning Candidate Details
| Candidate ID: | R1441 |
| Source ID: | DB12281 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Luspatercept |
| Synonyms: | Luspatercept; luspatercept-aamt |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Luspatercept is a recombinant fusion protein comprised of a modified extracellular domain of activin receptor type IIB fused to the FC domain of human IgG1. It was first approved for use in the United States in November 2019 under the brand name Reblozyl® for the treatment of anemia in patients with beta thalassemia who require regular blood transfusions. Luspatercept is novel in that it ameliorates anemia via action on late-stage erythropoiesis, in contrast to typical erythropoiesis-stimulating agents (ESAs), such as and , which act only on early-stage erythropoiesis. Luspatercept's novel mechanism of action, then, is uniquely suited for the treatment of conditions in which late-stage erythropoiesis is defective, such as beta thalassemia and other myelodysplastic diseases. |
| CAS Number: | 1373715-00-4 |
| Molecular Weight: | |
| DrugBank Indication: | Luspatercept is indicated for the treatment of anemia in adults with beta thalassemia who require regular red blood cell transfusions. |
| DrugBank Pharmacology: | Luspatercept binds to, and inhibits, several ligands that act as negative regulators of late-stage erythropoiesis, thereby alleviating the ineffective erythropoiesis observed in patients with beta thalassemia. Thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, ischemic stroke) have been reported in patients with beta thalassemia receiving luspatercept - patients with a greater baseline risk of thromboembolism may benefit from concomitant thromboprophylaxis while undergoing therapy with luspatercept. Luspatercept may carry some degree of embryo-fetal toxicity and should therefore be avoided in pregnancy. Women of child-bearing age should use an effective form of contraception during therapy and for 3 months after completion of therapy. |
| DrugBank MoA: | 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. |
| Targets: | -- |
| Inclusion Criteria: | Therapeutic strategy associated |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I16 | 6713 | Cerebrovascular disease | An vascular disease that is characterized by dysfunction of the blood vessels supplying the brain. http://en.wikipedia.org/wiki/Cerebrovascular_disease, http://www.ncbi.nlm.nih.gov/books/NBK378/ | disease of anatomical entity/ cardiovascular system disease/ vascular disease/cerebrovascular disease | Details |