|
Synonyms: ACE-536 | ACE536 | luspatercept-aamt | Reblozyl®
luspatercept is an approved drug (FDA (2019), EMA (2020))
Compound class:
Peptide or derivative
Comment: Luspatercept (ACE-536) is a fusion protein comprising human ACVR2B (activin receptor type 2B) extracellular domain (which is mutated to reduce activin binding), fused with human immunoglobulin G1 Fc fragment [2]. Mechanistically luspatercept acts as a ligand trap for growth/differentiation factor-11 (GDF11; and other Smad2/3-activating ligands), which reduces GDF11-induced Smad2/3 activation, and blocks the inhibitory effect of GDF11 on erythroid precursor maturation. Functionally, it promotes maturation of late-stage erythroid precursors, which is in contrast to erythropoietin, which stimulates proliferation of early-stage erythrocyte precursors. Using Gdf11 knockout, Guerra et al. (2019) dispute GDF11 as the molecular target of luspatercept and its proposed inhibitory effect on late erythropoiesis [1]. They do not propose an alternative mechanism of action.
|
Classification  |
|
| Compound class | Peptide or derivative |
| Approved drug? | Yes (FDA (2019), EMA (2020)) |
| International Nonproprietary Names |
|
| INN number | INN |
| 9823 | luspatercept |
| Synonyms |
| ACE-536 | ACE536 | luspatercept-aamt | Reblozyl® |
| Database Links |
|
| Specialist databases | |
| IMGT/mAb-DB | 487 |
| Other databases | |
| DrugBank Ligand | DB12281 |
| GtoPdb PubChem SID | 387065620 |
| Search PubMed clinical trials | luspatercept |
| Search PubMed titles | luspatercept |
| Search PubMed titles/abstracts | luspatercept |
