ACE-031 (ramatercept): what it is, what the trials found and why development stopped

Myostatin, also called GDF-8, is a protein made by muscle that signals through the activin type II receptors on muscle cells to hold muscle growth in check. Mice engineered to lack it, described by Se-Jin Lee’s laboratory at Johns Hopkins in 1997, grow muscles two to three times the normal size ^[17]. In 2005 the same laboratory showed that a soluble form of the activin receptor type IIB (ACVR2B), released from the cell and free to circulate, could cause dramatic muscle growth of up to 60% within two weeks when injected into normal mice ^[1]. The soluble receptor worked by binding myostatin before it could reach the real receptor. It also still worked, though less well, in mice with no myostatin at all, showing that it was blocking other muscle-limiting proteins too, such as activin A ^[1].

ACE-031 is the pharmaceutical version of that idea. Acceleron Pharma joined the outer, ligand-binding part of human ActRIIB to the Fc region of a human IgG1 antibody, producing a dimeric fusion protein that stays in the circulation for weeks and acts as a decoy for myostatin, activins and related ligands ^{[4] [2]}. Its generic name is ramatercept. It is one of a family of receptor-Fc fusion proteins from the same company: luspatercept is a modified ActRIIB-Fc, and sotatercept is the ActRIIA equivalent ^{[10] [11]}.

ACE-031 is not a peptide in the usual sense, although it is sold as “ACE-031 peptide”. It is a large glycosylated protein made in mammalian cells, closer to an antibody than to compounds such as BPC-157. It is grouped on this site with GDF-8 (myostatin) and follistatin 344 as myostatin pathway proteins, and it differs from growth hormone-axis compounds such as IGF-1 LR3 in acting on a completely separate pathway. See what research peptides are for how a discontinued drug candidate ends up on sale as a research chemical.

Myostatin and activin A belong to the TGF-beta family and signal by binding activin type II receptors on the muscle cell surface, which switches on Smad proteins that suppress muscle protein synthesis and growth. ACE-031 carries the same binding pocket as the natural receptor but floats free in the blood, so ligands bind to it instead and never reach the cell ^{[1] [2]}. Because it binds several ligands, not only myostatin, its effect in animals is larger than that of antibodies that neutralise myostatin alone ^[2]. That is the ACE-031 myostatin story in one sentence: a decoy receptor that removes myostatin and its relatives from the blood.

That breadth is also the source of its problems. Activins and related ligands have roles beyond muscle, including in blood vessels, red blood cell production, bone and the reproductive system, and a decoy receptor removes them from all those systems at once. The bone and fat effects seen in the human studies, and the blood vessel effects that ended development, follow from the same mechanism that builds muscle ^{[3] [4]}.

ACE-031 differs from follistatin, the other myostatin pathway protein sold online, in that follistatin is a natural binding protein that also neutralises activin and requires gene therapy or injected protein to deliver, whereas ACE-031 is an engineered receptor decoy with a long half-life. Our follistatin 344 guide covers that comparison.

The ACE-031 benefits claimed online, muscle growth and fat loss, do have animal support. In mice, 28 days of ACE-031 increased body weight by 16% over controls and the wet weights of individual leg muscles by 26% to 46%, with fibre cross-sectional area increasing in both slow (type I) and fast (type II) fibres, which distinguishes it from selective myostatin inhibition that mainly affects type II fibres ^[2]. In common marmosets, a non-human primate, 14 weeks of ACE-031 increased lean body mass compared with baseline, enlarged both fibre types in the biceps, and increased the absolute and specific force of an isolated muscle; this study was published in 2026, many years after clinical development stopped ^[5].

These are strong and reproducible animal results. The question was never whether ACE-031 builds muscle in animals, but whether it could be given to people at doses that build muscle without unacceptable effects elsewhere.

Healthy volunteers: the first-in-human study randomised 48 healthy postmenopausal women to a single subcutaneous dose of ACE-031 at 0.02 to 3 mg/kg or placebo, three to one. Exposure rose in proportion to dose, the half-life was 10 to 15 days, and the most notable adverse event was redness at the injection site. At day 29, the 3 mg/kg group showed a 3.3% increase in total body lean mass by DXA and a 5.1% increase in thigh muscle volume by MRI, both statistically significant, and blood markers suggested effects on bone and fat metabolism too ^[3]. The registry entry for this study, NCT00755638, lists it as completed with 48 participants between September 2008 and July 2009 ^[6]. A second study in healthy postmenopausal women, NCT00952887, enrolled 70 and is also listed as completed ^[7]; we found no separate publication of its results.

Duchenne muscular dystrophy: Acceleron then ran a randomised, double-blind, placebo-controlled, ascending-dose trial in ambulatory boys with Duchenne muscular dystrophy, giving ACE-031 under the skin every two to four weeks. The primary objective was safety. No serious or severe adverse events were attributed to the drug, but the study was stopped after the second dosing regimen because of potential safety concerns of epistaxis (nosebleeds) and telangiectasias (dilated small blood vessels visible in the skin). There were trends, none statistically significant, towards maintenance of six-minute walk distance in the treated groups compared with a decline on placebo, and towards increased lean mass and bone mineral density and reduced fat mass. The authors stated that non-muscle-related adverse events contributed to the decision to discontinue ^[4].

The registry entries confirm the outcome. NCT01099761, the main Duchenne study, started in April 2010, enrolled 24 boys and is listed as terminated “based on preliminary safety data” ^[8]. Its extension study, NCT01239758, started in October 2010, enrolled 11 and was terminated for the same reason ^[9]. Acceleron did not take ACE-031 forward, and the ACE-031 clinical trial programme for muscle disease ended there. The company is now a subsidiary of Merck ^[8].

In short, blocking all ActRIIB ligands at once produced measurable muscle gains in people, but the bleeding and vascular effects appeared before the muscle effects were large enough to matter clinically.

The ACE-031 results that matter are these. A single 3 mg/kg dose increased lean mass by about 3% and thigh muscle volume by about 5% in a month in healthy women ^[3]. In boys with Duchenne, repeated dosing produced trends in the hoped-for direction that did not reach significance before the study was stopped ^[4]. No study measured strength, performance or body composition in healthy men, in athletes or in anyone training, and no study ran for longer than a few months.

ACE-031 before and after claims from the black market have a further problem: the products usually do not contain ACE-031. In 2025, anti-doping researchers in Austria bought 14 black-market products labelled ACE-031. Twelve contained a protein that reacted with anti-ACVR2B antibodies, but analysis by mass spectrometry and immunoblotting showed it was the full-length human activin receptor IIB rather than the receptor-Fc fusion protein; none contained an Fc portion, and all contained many other proteins alongside the main one ^[10]. A full-length membrane receptor is not a decoy that works in the blood, so whatever effects users report cannot be attributed to ACE-031.

In the healthy volunteer study, single subcutaneous doses ranged from 0.02 to 3 mg/kg, and only the top dose produced significant changes in lean mass ^[3]. For a 70 kg person, 3 mg/kg would be 210 mg of protein in one dose, which is far beyond the 1 mg vials sold online. In the Duchenne trial the drug was given every two to four weeks in ascending dose cohorts; the paper does not report doses in its abstract, and the trial was stopped after the second regimen ^[4]. In mice, the dose in the 28-day study is given in the full paper rather than the abstract ^[2], and the black-market detection study in rats used 10 mg/kg ^[10].

These figures are reported for information, not as recommendations. The ACE-031 bodybuilding protocols found online, typically 1 mg every one to two weeks, are a tiny fraction of the only human dose that produced a measurable effect, and the vials they refer to have mostly been shown to contain the wrong protein ^[10]. The peptide calculator and the ACE-031 calculator page handle the arithmetic of dissolving a vial in bacteriostatic water, but no calculation can make 1 mg into 210 mg.

ACE-031 was given by subcutaneous injection in every human study, and the ACE-031 half-life of 10 to 15 days meant dosing every two to four weeks ^{[3] [4]}. Products sold online are freeze-dried powders in 1 mg vials for subcutaneous injection. As a large glycosylated protein made in mammalian cells, it cannot be made by peptide synthesis and would not survive oral use; oral or nasal ACE-031 products have no basis.

The main compound in black-market ACE-031 products had a mass of about 58.4 kDa on gel electrophoresis, which the Austrian group identified as full-length ACVR2B rather than the Fc fusion ^[10]. A genuine ACE-031 sample can be identified by its Fc portion, for instance by cleavage with the IdeS protease, which did not cut the black-market products ^[10].

The human safety record is short but specific. In healthy women, a single dose was generally well tolerated, with injection-site redness the main adverse event ^[3]. In boys with Duchenne given repeated doses, nosebleeds and telangiectasias appeared and were serious enough for the sponsor to stop the trial and its extension on preliminary safety data ^{[4] [8] [9]}. The authors attributed the decision to non-muscle-related adverse events of the drug itself ^[4], which follow from a mechanism that removes activin-family signalling from tissues beyond muscle.

Because ACE-031 binds activins, which help regulate red blood cell production, reproductive hormones and bone, the healthy volunteer study also saw changes in bone and fat biomarkers ^[3]. Longer-term effects were never studied because development stopped. The 2016 review of emerging muscle drugs relevant to doping listed ACE-031 among myostatin receptor ligand blockers of interest ^[11], and a 2023 anti-doping study noted that no drug candidate in this class has obtained approval while such compounds remain readily available for research purposes and on the black market ^[12].

For products bought online the composition is the larger risk. The 2025 analysis found that two of 14 products contained no ACVR2B-reactive protein at all, and the other 12 contained a full-length receptor with many contaminating proteins ^[10]. Injecting an unknown mammalian-cell protein preparation carries risks of immune reactions and contamination that have nothing to do with ACE-031’s own pharmacology. So whether ACE-031 is safe cannot be answered from the trials, and whether a vial labelled ACE-031 is safe cannot be answered at all.

ACE-031 is not approved as a medicine anywhere, and no application has been made; development was discontinued after the Duchenne trial. In sport, WADA prohibits agents preventing activin receptor IIB activation under section S4.3 of the Prohibited List, with ACE-031 specifically named, prohibited at all times ^{[10] [13]}. Anti-doping laboratories have adapted a method developed for luspatercept, another ActRIIB-Fc protein, to detect black-market ACE-031 in serum, and in rats it was detectable for up to 48 hours after a 10 mg/kg dose ^[10]. UK Anti-Doping applies the same list ^[14].

In the UK, ACE-031 has no marketing authorisation, and regulation 46 of the Human Medicines Regulations 2012 makes it an offence to sell or supply an unauthorised medicinal product ^[15]. It is not a controlled drug under the Misuse of Drugs Act 1971 ^[16]. See our UK legal status page, the US page and the legal status overview for other countries.

ACE-031 is a large glycosylated protein and is more fragile than a short synthetic peptide. It is sold freeze-dried and should be kept cold, dry and away from light; once reconstituted it should be refrigerated, not shaken, and not frozen and thawed repeatedly. The black-market products analysed in 2025 contained a high proportion of aggregated and contaminating proteins even before reconstitution ^[10]. See how to store peptides.

PepFinder does not sell ACE-031. You can compare ACE-031 prices, including UK listings and US listings, and filter for third-party tested suppliers.

For this product the published evidence is that most vials do not contain what the label says ^[10]. A meaningful certificate of analysis would need to show a protein of the right size on a gel, the presence of the IgG1 Fc portion, and results for endotoxin and host-cell proteins; an HPLC purity figure alone cannot distinguish ACE-031 from a full-length receptor or from any other protein. Read how to read a COA, third-party peptide testing and how to spot a fake peptide supplier. If muscle growth is the aim, our peptides for muscle growth page sets ACE-031 beside HGH and other compounds with human data.