OnePin Peptide Library · Muscle
ACE-031
ACE031 · ActRIIB-Fc · Activin Type IIB Receptor
ACE-031 (RAP-031) is a soluble decoy receptor fusion protein consisting of the extracellular domain of activin receptor type IIB (ActRIIB) fused to the Fc region of human IgG1. It functions as a 'trap' for myostatin (GDF-8) and related TGF-beta superfamily ligands (activin A, GDF-11), preventing those ligands from binding membrane-bound ActRIIB on muscle cells and thus de-repressing muscle hypertrophy. Developed by Acceleron Pharma originally for Duchenne muscular dystrophy and other muscle-wasting indications.
Same day each week. Inject into thigh or abdominal subcutaneous tissue. Reconstitute lyophilized vial gently with bacteriostatic water - do NOT shake. The Fc fusion protein is a large molecule (~80 kDa) - use larger-gauge needle (25-27g) for smooth injection.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
ACE-031 is a soluble form of the activin receptor type IIB (ActRIIB) fused to an IgG1 Fc domain. It functions as a circulating decoy that captures TGF-beta superfamily ligands - primarily myostatin (GDF-8), activin A, and GDF-11 - before they can bind membrane-anchored ActRIIB on skeletal muscle cells.
Myostatin Inhibition
Myostatin is the primary negative regulator of skeletal muscle mass. ACE-031's capture of circulating myostatin removes the brake on muscle growth, producing hypertrophy independent of training stimulus in animal models and human Phase 1 trials.
Activin A and GDF-11 Capture
ACE-031 also binds activin A (involved in inflammation, hematopoiesis, and reproductive endocrinology) and GDF-11 (controversial role in aging). Off-target binding to these ligands may explain some of the non-muscle adverse events that halted clinical development.
Fc Fusion Architecture
The IgG1 Fc domain provides FcRn-mediated half-life extension (similar mechanism to therapeutic monoclonal antibodies), giving ACE-031 a half-life of approximately 7-14 days vs the minutes-to-hours half-life of native peptides. This permits weekly to bi-weekly dosing.
Net Effect
Increased lean mass (typically 1-3% over weeks at therapeutic doses) and increased strength in animal models. Human Phase 1 data confirmed dose-dependent muscle mass increase before development was halted.
Vascular Side Effects
The DMD trial halt was driven by epistaxis (nosebleeds), telangiectasias (small dilated vessels), and gum bleeding - hypothesized to reflect off-target effects on activin signaling in vascular endothelium. This safety signal is the primary risk distinguishing ACE-031 from more targeted myostatin-only inhibitors (Follistatin, BMS-986089).
What to expect
Week 1-2: minimal subjective effect. Steady-state plasma exposure builds over first 4 weeks (long half-life).
Week 4-8: lean mass gains accumulate. Strength improvements measurable in trained users. Body composition changes detectable on DEXA.
Week 8-12: peak therapeutic effect. Lean mass changes plateau around 2-3% in non-DMD adults. Vascular surveillance ongoing - any new bleeding signal warrants discontinuation.
Evidence
Interactions & stacking
What's safe to combine, and what belongs in a separate pin.
Keep separate
Side effects & safety
Commonly reported
- Injection site reaction (large molecule, larger injection volume)
- Mild headache (early doses)
- Mild fatigue or muscle soreness (initial training response)
Less common & notes
- Epistaxis (nosebleeds) and telangiectasias (small dilated capillaries in skin) - the bleeding signal that halted the Phase 2 DMD trial.
- Gum bleeding.
- Thrombocytopenia (mild platelet decrease) seen in some trials.
- Theoretical anti-drug antibody formation (Fc fusion proteins can be immunogenic).
- Long-term safety beyond Phase 1 single-dose data not established.
- Reproductive effects unknown - activin axis is essential in pregnancy.
- Long-term cardiovascular outcomes unknown.
Pharmacokinetics
Storage. Lyophilized vial: refrigerate (2-8°C / 36-46°F) for short-term, freeze (-20°C) for long-term storage. Avoid freeze-thaw cycles - fusion protein sensitive. Light-sensitive. After reconstitution with bacteriostatic water: refrigerate, use within 7 days. Do NOT shake during reconstitution - swirl gently. Discard if cloudy, discolored, or contains particulates. The Fc fusion protein is more stability-sensitive than smaller native peptides.
Regulatory status
Not FDA-approved for any indication. Phase 2 clinical development halted in 2013 due to bleeding adverse events. Acceleron Pharma (now part of Merck) has pivoted to other ActRIIB-Fc-derivative therapeutics (luspatercept/Reblozyl approved 2019 for beta-thalassemia and MDS anemia; sotatercept/Winrevair approved 2024 for pulmonary arterial hypertension) which use refined targeting to reduce off-target activin pathway effects. ACE-031 itself remains an experimental research chemical. WADA prohibited under class S2 (peptide hormones, growth factors). Sale for human use is illegal in regulated jurisdictions.
Put it to work
Calculate, log & track
Open ACE-031 straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
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The guide & community
The complete ACE-031 walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
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