Compound reference
ACE-031
Also known as Ramatercept, ActRIIB-IgG1 Fc
ACE-031 (ramatercept) is a soluble ActRIIB-Fc fusion protein — a myostatin ligand trap that reliably builds muscle in animals and raised lean mass in early human trials. Its Duchenne program was halted when off-target BMP9/10 inhibition caused nosebleeds and dilated blood vessels.
- Molar mass
- ≈78 kDa (glycosylated Fc-fusion homodimer)
- Sequence
- Recombinant human ActRIIB extracellular domain fused to a human IgG1 Fc region
- Half-life
- ≈10–15 days (subcutaneous)
Investigational; clinical development discontinued after off-target safety events (bleeding, telangiectasia).
Mode of action
ACE-031 is not a peptide in the usual sense — it is a recombinant fusion protein that joins the extracellular ligand-binding domain of the human activin receptor type IIB (ActRIIB) to the Fc region of human IgG1. The Fc half makes it a large, long-lived antibody-like molecule (a glycosylated dimer of roughly 78 kDa); the receptor half is the business end.
It works as a decoy, or ligand trap. ActRIIB normally sits on the muscle-cell surface and receives myostatin — the body's main brake on muscle growth — along with related ligands such as GDF11 and the activins. ACE-031 floats free in the circulation and soaks up those same ligands before they can reach the real receptor, releasing the brake and allowing muscle to grow. Crucially, the trap is not perfectly selective: the ActRIIB domain also binds bone morphogenetic proteins BMP9 and BMP10, which regulate blood-vessel integrity. That off-target binding turned out to be the molecule's undoing.
Main intended effect
To increase skeletal muscle mass and, by extension, strength and physical function — the rationale being to treat diseases of muscle wasting, with Duchenne muscular dystrophy as the lead indication.
Areas of interest
The clinical focus was Duchenne muscular dystrophy. The same myostatin-inhibition logic has been raised for other muscle-loss settings — sarcopenia, cancer cachexia, and disuse atrophy — and the muscle-building potential also makes ACE-031 a target of anti-doping surveillance. It was developed by Acceleron Pharma (the research code carries through to the name ramatercept).
Evidence for intended effects
The muscle effect itself is well supported. In mice, the soluble ActRIIB-Fc construct increased muscle wet weights and raised body weight by about 16%, and the growth was independent of fiber type. A single-ascending-dose Phase 1 study in healthy postmenopausal women increased lean mass and showed the long 10–15-day half-life expected of an Fc-fusion protein. A randomised, placebo-controlled Phase 2 trial in ambulatory boys with Duchenne muscular dystrophy then saw trends toward increased lean mass, decreased fat mass, higher bone mineral density, and maintained walking distance.
But that Phase 2 trial was stopped early, before efficacy could be established — and the reason matters more than the trends. Boys on ACE-031 developed nosebleeds (epistaxis), gum bleeding, and telangiectasia (small dilated blood vessels), adverse effects traced to the molecule's cross-inhibition of BMP9 and BMP10. So the honest summary is two-sided: the drug did what it was designed to do to muscle, and was discontinued for what it did everywhere else.
| Strand | What exists | Tier |
|---|---|---|
| Preclinical muscle growth | Mice: increased muscle mass, fiber-type independent | Strong preclinical |
| Healthy-volunteer Phase 1 | Single-ascending-dose: increased lean mass, ~10–15 day half-life | Phase 1 |
| Duchenne muscular dystrophy | Phase 2 RCT: lean-mass / bone trends, but terminated early | Phase 2 (halted) |
| Specificity / safety | Bleeding + telangiectasia from BMP9/10 cross-binding | Established (program-ending) |
Studied amounts (literature dosing context)
The human trials used subcutaneous injection at ascending dose levels in Phase 1 (healthy volunteers) and Phase 2 (Duchenne muscular dystrophy), exploiting the long half-life for infrequent dosing. These are study amounts from investigational trials that were not completed; there is no approved dose, and this page does not provide dosing guidance.
Safety and regulatory status
The defining safety problem is mechanistic, not incidental. Because ACE-031 traps BMP9 and BMP10 in addition to myostatin, and those proteins maintain vascular integrity, recipients developed nosebleeds, gum bleeding, and telangiectasia. Those signals stopped the Duchenne Phase 2 trial early, and clinical development of ACE-031 was subsequently discontinued. The episode is now a textbook caution about the lack of specificity of receptor-based ligand traps.
ACE-031 is not an approved medicine in any jurisdiction, and its development has ended. It is prohibited under World Anti-Doping Agency rules for its muscle-building potential, and seized black-market material has been characterised by anti-doping laboratories. As a complex recombinant glycoprotein, anything sold online as "ACE-031" is even harder to manufacture and verify than a short synthetic peptide — its identity, integrity, and purity are not assured.
Sources
A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers
Single-ascending-dose, randomized, placebo-controlled Phase 1 study (Attie and colleagues, Muscle & Nerve, 2013) of ACE-031 in healthy postmenopausal women. ACE-031 is a recombinant fusion protein of the extracellular domain of the human activin receptor type IIB (ActRIIB) linked to the Fc region of human IgG1; it acts as a ligand trap, binding ActRIIB ligands including myostatin, GDF11, and activins to block their signaling. A single dose increased lean mass, with a long mean half-life of 10-15 days and dose-proportional exposure.
Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial
Randomized, double-blind, placebo-controlled, ascending-dose Phase 2 trial (Campbell and colleagues, Muscle & Nerve, 2017) of subcutaneous ACE-031 (an ActRIIB-IgG1 Fc fusion protein) in ambulatory boys with Duchenne muscular dystrophy. The study observed trends toward increased lean mass, decreased fat mass, increased lumbar bone mineral density, and maintained 6-minute walk distance, but it was stopped early and did not establish efficacy. The early termination was driven by safety signals.
Challenges and future prospects of targeting myostatin/activin A signaling to treat diseases of muscle loss and metabolic dysfunction
Review (Lee, Bhasin, Klickstein and colleagues, Journals of Gerontology, 2023) of myostatin/activin-A signaling as a target for muscle-loss and metabolic disease. It defines ACE-031 as a decoy ActRIIB receptor — an extracellular ligand-binding domain fused to an immunoglobulin Fc domain — that traps myostatin, GDF-11, activins, and certain BMPs. It reports that the ACE-031 trial in Duchenne muscular dystrophy was terminated early after epistaxis and telangiectasias, likely caused by the molecule's binding of BMP-9, illustrating the off-target liability of non-selective ligand traps.
Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type
Preclinical study (Cadena and colleagues, Journal of Applied Physiology, 2010) showing that ACE-031 — a soluble ActRIIB extracellular region fused to human IgG Fc — significantly increased muscle wet weights (soleus, plantaris, gastrocnemius, EDL) and body weight (about 16% greater) in C57BL/6 mice. The growth was independent of fiber type, consistent with inhibiting negative regulators of skeletal muscle broadly rather than selective myostatin blockade.
Myostatin inhibitors: panacea or predicament for musculoskeletal disorders?
Review (Suh and Lee, Journal of Bone Metabolism, 2020) of myostatin inhibitors for musculoskeletal disorders. It identifies ACE-031 as a soluble ACVR2B receptor developed by Acceleron Pharma for Duchenne muscular dystrophy, and notes that its clinical development was prematurely terminated due to bleeding events (nosebleed, gum bleeding) and telangiectasia attributed to cross-inhibition of BMP9/10 — a recurring lack-of-specificity problem for ligand-trap myostatin inhibitors.
Gel Electrophoretic Detection of Black Market ACE-031
Anti-doping analytical study (Reichel and colleagues, Drug Testing and Analysis, 2025) characterizing black-market ACE-031, described as a dimeric fusion protein of a human activin receptor IIB fragment linked to an Fc part of human IgG1. The work used gel electrophoresis, Western blotting, and mass spectrometry to detect and analyze seized products, and notes that ACE-031 is prohibited under World Anti-Doping Agency regulations because of its muscle-building, performance-enhancing potential.