A doping laboratory tested 14 products sold as ACE-031. None of them contained ACE-031.

Why this note exists

ACE-031 is a research-market compound where a laboratory has bought the vials, opened them and published what was inside. In October 2025, Drug Testing and Analysis published an open-access analysis from the Seibersdorf doping control laboratory in Austria and the German Sport University Cologne, written because ACE-031 is prohibited in sport and laboratories need a way to detect it.[1] Detecting it meant buying it, and buying it meant discovering what is being sold.

This note sets out three separate things and keeps them separate: what that laboratory found in the products, what the registered human trials actually measured and why they stopped, and where ACE-031 stands with FDA today. A note on scope: the 14 products tested are the ones that laboratory bought from unnamed sources, and nothing in the study describes any vendor pepmg tracks or any vial any reader owns.[1]

The product analysis

Twelve vials, one wrong protein, eleven purification tags

The authors ran all 14 products on SDS-PAGE. Twelve produced a near-identical pattern with a main band around 58.4 kDa, and the products were, in the paper's words, "very impure," carrying many other proteins alongside the main one.[1] An antibody against the N-terminal region of ACVR2B bound the protein in those twelve, so an antibody test on its own would have read them as ACVR2B-positive.[1]

Mass spectrometry said otherwise. The twelve contained the full-length human activin receptor IIB, and not the receptor fragment fused to an antibody Fc that ACE-031 is.[1] The analysis found no IgG1 Fc peptides, and it did find many peptides from the receptor's cytoplasmic region, which ACE-031 does not contain.[1] The authors confirmed the absence of the Fc by digesting the products with IdeS protease, an enzyme that cuts immunoglobulins below the hinge and releases the Fc fragment: the approved ActRIIB-Fc drug used as a positive control was cut, and "no cleavage was observed for the BM products."[1]

Two details point at how the material was made. The observed mass matched the calculated mass of non-glycosylated ACVR2B without its signal peptide, 55.9 kDa, which the authors say "indicates that the BM products were produced in bacterial rather than mammalian expression systems. Otherwise, their mass would be higher."[1] And an anti-histidine blot found that all but one of the twelve still carried the histidine purification tag used to pull recombinant protein off a column, a residue of manufacture that the clinical molecule does not have.[1]

All figures as reported by Reichel and colleagues, who bought the products in the UK, Europe, China and the USA and kept the sources anonymous.[1]

The study's own purpose was detection, not consumer protection, and it delivered that: the authors showed a method built for the approved drug luspatercept also picks up these products in serum, and dosed rats to establish a detection window, because "administering black market products to human subjects was not ethically justifiable."[1] The rats received a single subcutaneous injection at 10 mg per kilogram of body weight and the protein was detectable for up to 48 hours; the authors note that the dose was relatively high and that the window in humans may differ.[1]

The molecule

ACE-031 is a glycosylated dimeric protein, and the market sells it by the milligram as a peptide

The paper describes ACE-031 as "a soluble homodimeric fusion protein (ActRIIB-IgG1Fc, 343 amino acids) with three N-glycosylation sites," held together by two interchain disulfide bridges and folded with seven intrachain ones.[1] It works by acting as a decoy, trapping myostatin and related ligands before they reach the real receptor.[1]

What a regulated version of that molecule class looks like is on a label. Reblozyl (luspatercept-aamt), whose original BLA 761136 submission carries an approval date of November 8, 2019 in Drugs@FDA, is described in its prescribing information as "a receptor fusion protein consisting of a modified extracellular domain of the human activin receptor type IIB linked to a human IgG1 Fc domain with a calculated molecular mass of approximately 76 kD," and it is "produced in Chinese hamster ovary cells by recombinant DNA technology."[12][13] It ships as 25 mg and 75 mg single-dose vials of lyophilised powder, reconstituted before subcutaneous injection, and it is approved for anemia in beta thalassemia and certain myelodysplastic syndromes — a blood indication, not a muscle one.[12]

Now the research market. In pepmg's own price index, generated October 8, 2026, seven tracked vendors list ACE-031, six as a single 1 mg vial and one as a 6 mg vial, at listed prices from $69.99 to $173, and one of them names the product "ACE-031 Peptide."[18] A 343-residue glycosylated homodimer is not a peptide in the sense that word is used on those pages, and the trials below dosed by body weight, per kilogram, not by vial. pepmg makes no claim about what is in any particular vendor's vial; we have not tested one.

The human record

Four trials, 153 people, finished in 2011

A ClinicalTrials.gov search for ACE-031 on October 8, 2026 returned four studies, all sponsored by Acceleron Pharma, whose record now carries the sponsor name "Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc."[10] Their enrolments add to 153 people, and the latest completion date among them is June 2011.[5][6][7][9]

A fourth study, NCT01239758, an 11-boy open-label extension, was also terminated on preliminary safety data and has no posted results.[9]

The single published healthy-volunteer study is the one most often quoted. Forty-eight healthy postmenopausal women were randomised 3 to 1 to one subcutaneous dose of ACE-031 between 0.02 and 3 mg per kilogram of body weight, or placebo.[3] At day 29, the authors report statistically significant increases in the 3 mg/kg group only: mean total body lean mass up 3.3% by DXA and thigh muscle volume up 5.1% by MRI, both at P = 0.03.[3] Half-life was 10 to 15 days and adverse events included injection site erythema.[3] That is one dose, in one dose group of a 48-person dose-escalation study, measured at 29 days, in postmenopausal women. Those doses are given here as the paper published them, per kilogram; pepmg does not convert a per-kilogram research dose into an amount.

The 70-woman multiple-dose study is the gap in the record. It completed in February 2011, its registry entry has not been updated since March 2011, no results are posted, and a PubMed search for ACE-031 on October 8, 2026 — which returned 12 records in total, of which two report human trials — turned up no publication of it.[6][19] Repeat dosing in healthy adults is exactly the question the research market is answering for itself, and the study that asked it has never reported.

Why it stopped

Nosebleeds and spider veins in 5 of 9 boys, and a cohort that never enrolled

The Duchenne phase 2 randomised 24 ambulatory boys: 9 to 0.5 mg/kg every four weeks, 9 to 1.0 mg/kg every two weeks and 6 to placebo, for 12 weeks of treatment inside a 24-week study.[7][8] A third cohort at 2.5 mg/kg every four weeks is listed in the posted results with zero participants and the comment "Study terminated prior to enrolling cohort 3."[8]

Its primary outcomes were adverse reactions and laboratory adverse reactions, not muscle or walking.[7] On the first of those, the posted results record adverse reactions in 1 of 9 boys on the lower regimen, 6 of 9 on the higher one and 0 of 6 on placebo, with no serious adverse events in any arm.[8] The events that ended the programme are itemised in the same posting.

The published paper states the same thing in fewer words: ACE-031 "was not associated with serious or severe adverse events," and "[t]he study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias."[4] Both Duchenne records — the core study and the extension — carry the registry's own reason for stopping: "based on preliminary safety data."[7][9]

The efficacy signals people quote from this trial were all secondary, and the posted numbers are thinner than the retellings. Total lean body mass rose a mean 3.6% and 4.1% in the two ACE-031 arms — and 2.6% on placebo, in growing boys, with standard deviations of 1.3 to 1.8.[8] Hand-held myometry showed no clear separation: knee extension strength fell in every arm, posted as a mean change of −3.6 and −3.3 on ACE-031 against −3.7 on placebo, in a measure the registry labels percent change from baseline.[8]

Six-minute walk distance is the number that travels. The registry posts it split into two age strata without giving how many boys fell in each, inside arms of 9, 9 and 6. Among boys aged 10 or older it reads +4.5 m and −3.2 m on ACE-031 against −47.6 m on placebo; among boys under 10 it reads +43.8 m, +2.5 m and +5.2 m.[8] The apparent separation in the older stratum rests on a placebo decline measured in a fraction of six boys, and every cell carries a standard deviation between 23.6 and 61.5 m.[8] The published paper calls it a trend that was "not statistically significant."[4]

Since then

The newest ACE-031 paper is about marmosets

Fifteen years after the last human dose in a registered trial, the most recent ACE-031 publication returned by a PubMed search on October 8, 2026 is a primate study.[19] PLOS ONE published it on February 13, 2026, from authors including former Acceleron staff alongside academic collaborators; a preprint appeared on bioRxiv in October 2025.[11] Common marmosets were randomised to ACE-031 or a buffer vehicle for 14 weeks; the animals on ACE-031 gained lean body mass over the period while vehicle controls did not, biceps fibre cross-sectional area increased for both fibre types, and isolated muscle produced more force ex vivo.[11] The authors conclude that efficacy in non-human primates "provides optimism" for treating human myopathies.[11]

It is an animal study, and it does not change the human record. The competing-interests statement notes that co-authors were former employees of the company that holds the patent. No new ACE-031 trial has been registered: the four on the registry all began between 2008 and 2010.[10]

Where it stands with FDA

Not approved, and not on the compounding agenda either

An openFDA query of the Drugs@FDA data and of drug labels on October 8, 2026 returned no application and no label for ACE-031 or ramatercept.[14] The doping laboratory's paper puts it plainly from the other side: "So far, no approved ACE-031 pharmaceuticals are available."[1]

The compounding question is separate, and the answer there is also no. FDA sorts substances nominated under section 503A into three categories, and maintains a page for the ones it considers to raise significant safety concerns.[15] That page, current as of April 22, 2026, carries a 14-substance category 2 table and a second list of nominations that were withdrawn, and ACE-031 appears in neither — the peptides in the category 2 table are GHRP-2, GHRP-6, ibutamoren mesylate, ipamorelin acetate and kisspeptin-10.[16] ACE-031 was not one of the seven substances the Pharmacy Compounding Advisory Committee considered on July 23-24, 2026, and it is not one of the five FDA has named for the committee's next meeting.[17][2] Those negatives are bounded to those FDA pages and to openFDA, read on October 8, 2026.

On sport, the authors of the product analysis — who work in a doping control laboratory and in the European Monitoring Center for Emerging Doping Agents — write that ACE-031 is prohibited under sub-chapter S4.3 of the WADA List, citing the 2024 edition.[1] The current List says the same by name: WADA's 2026 Prohibited List, in force since January 1, 2026, gives "Decoy activin receptors (e.g. ACE-031)" as an example under S4.3, agents preventing activin receptor IIB activation, prohibited at all times, and the same section lists follistatin among myostatin-binding proteins.[20]

Four things this note is not saying

It is not saying any particular vendor's vial contains the wrong protein. Fourteen products bought by one laboratory from unnamed sources is what was tested, and the paper names no seller.[1] What it establishes is that the failure mode exists and was common in that sample.

It is not saying ACE-031 does nothing. In the 3 mg/kg group of a 48-person single-dose study it increased lean mass and thigh muscle volume against placebo, and in marmosets it increased muscle mass and force.[3][11]

It is not saying the Duchenne trial proved harm. No serious adverse events were posted, the bleeding events were nosebleeds and visible small vessels, and the study was stopped as a precaution before the top dose cohort enrolled.[4][8]

And it is not giving a dose or a protocol. The per-kilogram figures here are trial doses in the populations that received them, reported with their source, and nothing on this page is medical advice.

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