ACE-031
Soluble activin receptor type IIB / IgG1 Fc fusion protein · Ramatercept · ActRIIB-Fc · ACVR2B-Fc · ACE031
Myostatin and activin decoy receptor; human trials were halted over bleeding side effects.
Typical dose
1 mg
Once weekly
Range
1–3
mg
Half-life
12.5 days
see Dosing
Evidence
Early human
Subcutaneous
What it is
ACE-031 is not a peptide. It is a large fusion protein built from the extracellular ligand-binding domain of the activin type IIB receptor joined to the Fc region of human IgG1, developed by Acceleron Pharma as a treatment for Duchenne muscular dystrophy. It works as a decoy: it soaks up the ligands that would otherwise dock on the real receptor.
It got further in humans than almost anything else in this category. A single-ascending-dose study in 48 healthy postmenopausal women (0.02-3 mg/kg subcutaneously) produced a statistically significant 3.3% rise in total body lean mass and a 5.1% rise in thigh muscle volume at day 29 in the top 3 mg/kg cohort, with serum biomarker changes suggesting effects on bone and fat metabolism, and a Phase 2 trial in ambulatory boys with DMD showed trends toward preserved walking distance, increased lean mass and bone mineral density, and reduced fat mass.
Both programmes were stopped. The activin type IIB receptor also binds BMP-9 and BMP-10, which maintain blood vessel integrity, and trapping them produced nosebleeds, gum bleeding and skin telangiectasias. That is a mechanism-linked effect, not a manufacturing problem, and it does not go away by lowering the dose to grey-market levels.
How it works
Myostatin, activin A and several related TGF-beta family ligands suppress muscle growth by signalling through activin type II receptors on the muscle cell surface. ACE-031 presents a soluble copy of that receptor's binding domain into the bloodstream, so circulating ligands bind the decoy instead of the membrane receptor. The brake on Smad2/3 signalling is released and muscle mass increases.
The Fc portion does two jobs: it makes the molecule a dimer, doubling its ligand-binding sites, and it recycles through the neonatal Fc receptor, which is why the half-life is measured in weeks rather than hours. The same lack of selectivity that makes it powerful is what caused the vascular problems, because the receptor domain does not distinguish myostatin from BMP-9 and BMP-10.
Dosing
These are grey-market numbers, not clinical ones. Trials dosed 0.02-3 mg/kg subcutaneously, and the only cohort with a statistically significant lean-mass gain was the top 3 mg/kg group (+3.3% lean mass, +5.1% thigh muscle volume at day 29), which for an 80 kg adult is about 240 mg per injection. A 1 mg vial is a small fraction of even the lowest cohort, and matching trial exposure is neither affordable nor sensible given why the trials stopped.
Reconstitution calculator
Pre-loaded with ACE-031’s vial size, water volume and typical dose. Change anything.
Typical: 1 mg · range 1–3
Draw to
100 u
1 mL · 1 mg
Concentration
1 mg/mL
10 mcg per unit
Doses per vial
1
Vial lasts
7 days
CheckThe draw fills more than 90% of the barrel. Workable, but there is no room for an air bubble or a correction.
Once mixed
Refrigerate at 2-8C and use within 7-14 days. Never freeze the reconstituted solution and discard it if it turns cloudy or shows visible particles, which indicates aggregation.
1 mL of bacteriostatic water into a 1 mg vial gives 1 mg/mL, so a 1 mg dose is the full 100 units of a U-100 insulin syringe. This is a large glycosylated fusion protein: add water slowly against the vial wall, swirl until clear, and do not shake, as agitation causes aggregation that both destroys activity and raises immunogenicity.
Storage
Before mixing
Store at -20C or below; the dry protein holds around 12 months and should not be repeatedly freeze-thawed.
After mixing
Refrigerate at 2-8C and use within 7-14 days. Never freeze the reconstituted solution and discard it if it turns cloudy or shows visible particles, which indicates aggregation.
Reported benefits
- ▪Dose-dependent increases in lean body mass in a Phase 1 human study
- ▪Reductions in fat mass alongside the lean mass gains
- ▪Trend toward increased bone mineral density in the DMD Phase 2 trial, not statistically significant
- ▪Trend toward preserved six-minute walk distance in ambulatory DMD patients
- ▪Traps multiple growth-suppressing ligands rather than myostatin alone
- ▪Half-life of 10-15 days means infrequent dosing
Side effects
- ▪Epistaxis (nosebleeds) and gum bleeding, the adverse events that ended the trials
- ▪Skin telangiectasias, visible dilated surface blood vessels
- ▪Headache, reported across dose cohorts
- ▪Injection-site erythema and reaction
- ▪Suppression of FSH through activin blockade, with unclear reproductive consequences
- ▪Antibody formation against the fusion protein, neutralising it and potentially cross-reacting
- ▪Effects persist for weeks after the last dose because of the long half-life
Do not use if
- ▪Any bleeding disorder, or use of anticoagulant or antiplatelet therapy
- ▪Personal or family history of hereditary haemorrhagic telangiectasia or other vascular malformation
- ▪Planned surgery or dental work within the following month
- ▪Active malignancy, given systemic blockade of a growth-suppressive pathway
- ▪Pregnancy or attempts to conceive
Evidence level — Early human
Small or early-phase human studies only.
Development was discontinued after Phase 2 and it has never been approved in any country; grey-market vials are sold as research chemicals.
Commonly run with
ACE-031 FAQ
Why were the trials really stopped?+
Nosebleeds, gum bleeding and skin telangiectasias in both the healthy-volunteer multiple-dose study and the DMD Phase 2 study. The activin IIB receptor domain also traps BMP-9 and BMP-10, which maintain blood vessel integrity, so the effect is built into the mechanism.
Is a 1 mg dose safer because it is so much lower than the trial doses?+
Lower exposure means lower risk of the vascular effects, but it also means the doses circulating in bodybuilding are far below anything shown to change body composition in humans. You are most likely getting neither the benefit nor a meaningful test of the risk.
How long does it stay in my system?+
With a half-life of roughly 10-15 days, a single dose takes about two months to clear substantially. If side effects appear you cannot simply stop and expect them to resolve quickly, which is a real difference from short-acting peptides.
How does it compare to follistatin?+
ACE-031 has real human pharmacokinetics, human efficacy signals and a documented failure mode. Follistatin has stronger animal data but no human evidence for the injectable protein. They act on the same axis, so combining them compounds the same vascular and FSH-related risks.
Will it show on a drug test?+
Myostatin inhibitors are prohibited at all times under the WADA code and dedicated assays for ActRIIB-Fc type molecules exist. Its multi-week half-life makes the detection window far longer than for short peptides.
References
- 1.A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers — Muscle & Nerve (2013) PMID 23169607
- 2.Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial — Muscle & Nerve (2017) PMID 27462804
- 3.Regulation of muscle growth by multiple ligands signaling through activin type II receptors — Proceedings of the National Academy of Sciences (2005) PMID 16330774
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