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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.
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Peptide Sequence  |
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ETRECIYYNANWELERTNQSGLERCEGEQDKRLHCYASWRNSSGTIELVKKGCWDDDFNCYDRQECVATEENPQVYFCCC EGNFCNERFTHLPEAGGPEVTYEPPPTGGGTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHYTQKSLSLSPGK |
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