Last updated: March 2026
ACE-031 (ActRIIB-Fc) is a soluble decoy receptor engineered by Acceleron Pharma to intercept myostatin, activin, and GDF-11 before they can suppress muscle growth. Phase 2 trials in Duchenne muscular dystrophy demonstrated rapid gains in lean mass and muscle volume — until vascular off-target effects forced a halt.
ACE-031 is an engineered fusion protein combining the ligand-binding domain of ActRIIB with an IgG1 Fc region for extended half-life. It acts as a circulating decoy receptor, capturing myostatin and related TGF-β family members before they reach muscle tissue — effectively derepressing muscle growth signaling at the pathway level.
ACE-031 consists of the extracellular domain of activin receptor type IIB (ActRIIB) fused to a human IgG1 Fc region. Injected subcutaneously, it circulates in blood and binds target ligands with high affinity — acting as a soluble decoy that competes with cell-surface ActRIIB on muscle fibers. The Fc fusion extends plasma half-life from hours to days, enabling monthly or less-frequent dosing.
Unlike antibodies targeting only myostatin (GDF-8), ACE-031 binds multiple ActRIIB ligands: myostatin, activin A, activin B, GDF-11, and BMP-9/10. This broad-spectrum capture accounts for its potent anabolic effect — but also explains the vascular side effects, since activin and BMP signaling plays roles in endothelial and vascular smooth muscle homeostasis.
Myostatin normally binds ActRIIB on muscle cells, activating the Smad2/3 signaling cascade, which suppresses protein synthesis and promotes atrophy. ACE-031 sequesters myostatin before receptor binding, effectively silencing Smad2/3 inhibition. This shifts the balance toward Smad1/5/8 (anabolic) signaling and allows IGF-1/PI3K/Akt pathways to drive hypertrophy and fiber size without the myostatin brake.
Follistatin is an endogenous binding protein that inhibits activins and myostatin through direct ligand sequestration, but also potently neutralizes FSH-stimulating activins in the hypothalamic-pituitary axis. ACE-031 is receptor-based and more selective for ActRIIB ligands, with no FSH-axis interference. In practice, ACE-031 produced faster and larger lean mass gains than follistatin 344 in comparative preclinical models — at the cost of broader vascular off-target effects.
Data from Acceleron Pharma's Phase 2 clinical trials in Duchenne muscular dystrophy and preclinical muscle-wasting models. Human trial data is from small cohorts — interpret with appropriate caution.
Research and reconstitution supplies for peptide protocols.
Dosing schedules, interaction warnings, and cycle protocols for 50+ compounds — all in one place.
This page is for educational and research purposes only. It is not medical advice. ACE-031 (ActRIIB-Fc) is not FDA approved for human use. Development was halted by Acceleron Pharma due to adverse vascular events in clinical trials. Research data cited is from small Phase 2 trials; treat all findings as preliminary. Always consult a qualified physician before considering any experimental compound.