Also known as: ActRIIB-Fc, Activin Receptor Type IIB Fusion Protein
Half-life: ~10-15 days (Fc-fusion)
Last reviewed: · Published:
ACE-031 is a recombinant fusion protein composed of the extracellular domain of the human activin type IIB receptor (ActRIIB) linked to the Fc portion of an IgG antibody. It works as a "ligand trap": by binding myostatin (GDF-8), activin A, GDF-11, and other TGF-β superfamily ligands in circulation, it prevents them from activating the ActRIIB receptor on muscle cells. The result is a net release of myostatin's tonic inhibition of muscle growth, producing rapid increases in muscle mass and strength in preclinical models.
ACE-031 was developed by Acceleron Pharma in collaboration with Shire as a clinical candidate for Duchenne muscular dystrophy (DMD). Early-phase trials in healthy volunteers showed significant increases in lean mass and thigh muscle volume after just one to four doses. However, the Phase 2 trial in DMD boys was halted in 2011 after several participants developed minor capillary leak (gum bleeding, mild nosebleeds) — likely an off-target consequence of trapping the ActRIIB ligands that also regulate vasculature. The program was discontinued.
ACE-031 remains one of the most thoroughly studied myostatin pathway inhibitors and is widely sold by research-chemical vendors. It is biologically distinct from synthetic short-peptide myostatin inhibitors (which usually fail to produce comparable effects) because it is a full recombinant biologic with high binding affinity. Researchers should be aware that the capillary leak signal observed in the DMD trial is a real safety concern, not an idiosyncrasy.
ACE-031 was developed in the late 2000s by Acceleron Pharma, a Cambridge MA biotech focused on TGF-β superfamily therapeutics. The Phase 1 trial in healthy postmenopausal women, published in Muscle & Nerve in 2013, demonstrated dose-dependent increases in lean mass after single doses. The Phase 2 trial in pediatric DMD patients began in 2010 but was suspended in 2011 following the capillary leak observations. Acceleron later pivoted its myostatin work into related programs (notably luspatercept/Reblozyl, an ActRIIB ligand trap for anemia, which was eventually approved). ACE-031 itself was never advanced past Phase 2.
Short-term tolerability in the Phase 1 healthy-volunteer trial was acceptable, with the principal adverse events being injection-site reactions and headache. The decision to halt the Phase 2 DMD program after observing mild bleeding suggests the safety margin is narrower than for peptide-based GH secretagogues, and that ActRIIB ligand trapping has off-target consequences for vascular integrity that may scale with cumulative dose. Researchers using ACE-031 should monitor for unusual bleeding and avoid it in subjects with vascular fragility.
Dose Range
0.5-3 mg/kg
Frequency
IV or SubQ every 2-4 weeks
Duration
Per protocol
Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.
Typical Vial Size
1 mg
Water Type
Bacteriostatic water (BAC water)
Mixing Volume
1 mL
Half-Life
~10-15 days (Fc-fusion)
Molecular Weight
~90 kDa
Reconstitute gently — avoid shaking, which can denature the Fc-fusion protein. Store at 2-8°C and use within 7-14 days for best activity.
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FDA Status
Not FDA approved. Clinical development halted in 2011 after capillary leak observations.
Legal Status
Unregulated research chemical. Prohibited by WADA.
USA
Not approvedClinical development discontinued by Acceleron
EU
Not approvedNot authorized as medicinal product
UK
Not approvedClassified as research chemical
Australia
Not approvedTGA has not authorized
Canada
Not approvedNot authorized for human use
Morrison BM, Lachey JL, Warsing LC, Ting BL, Pullen AE, Underwood KW, Kumar R, Sako D, Grinberg A, Wong V, Colantuoni E, Seehra JS, Wagner KR
Experimental Neurology (2009)
Preclinical study demonstrating that soluble ActRIIB-Fc (the prototype of ACE-031) improved muscle function and survival in an SOD1-ALS mouse model, supporting development of myostatin-pathway inhibitors for neuromuscular disease.
View Study →Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML
Muscle & Nerve (2013)
First-in-human Phase 1 study showing single doses of ACE-031 produced dose-dependent increases in lean mass and thigh muscle volume with acceptable short-term tolerability.
View Study →Whittemore LA, Song K, Li X, et al.
Biochemical and Biophysical Research Communications (2003)
Foundational study establishing that pharmacological inhibition of myostatin in adult animals produces rapid muscle hypertrophy, providing the rationale for the entire ActRIIB ligand-trap drug class including ACE-031.
View Study →Endogenous activin/myostatin binding protein — the gene-therapy myostatin inhibitor.
Short-peptide myostatin inhibitor targeting the GDF-8 / activin RIIB pathway.
Long-acting IGF-1 analog with reduced binding-protein affinity for sustained signaling.
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