ACE-031

Dosing from the Literature

Published for muscle growth: one dose of 0.02–3 mg/kg under the skin, given to three in four women in a placebo-controlled trial of 48 healthy postmenopausal women, and 0.5 mg/kg every 4 weeks or 1.0 mg/kg every 2 weeks for 12 weeks in 18 of 24 boys with Duchenne muscular dystrophy (Attie et al., 2013; Campbell et al., 2017). Not published: any dose in men, in athletes or beyond 12 weeks — the 70-woman multiple-dose study and the 24-week extension never reported their results (NCT00952887; NCT01239758).

The table records doses as each study gave them, with the population each was given to. Every human dose went under the skin, and the last of these trials ended in June 2011 (Attie et al., 2013; Campbell et al., 2017; NCT01099761).

What It Is

ACE-031 is not a peptide. It is a fusion protein, a piece of a human receptor stitched to a piece of a human antibody: residues 20–134 of the activin receptor type IIB precursor — the part that normally sits outside the cell and catches signals — then a three-glycine linker, then the hinge and the CH2-CH3 tail of human IgG1, 343 amino acids in all, with two identical chains locked together by two disulfide bridges (WHO INN List 108, 2012). The FDA substance registry gives its calculated mass as about 77,500 Da for the pair, before the sugars that three N-glycosylation sites per chain carry, and records its international nonproprietary name, ramatercept, under the CAS registry number 1169766-01-1 (FDA substance registry). KEGG lists its intended action as myostatin inhibition (KEGG DRUG D10347). For its 2010 mouse study Acceleron made it in Chinese hamster ovary cells carrying the fusion gene and purified it on a protein A column, which grips the antibody tail (Cadena et al., 2010).

The idea behind it is older than the molecule. Myostatin is a protein muscle makes to limit its own growth; animals and people who lack it are unusually muscular, and drugs that block it were expected to help in muscle-wasting disease (Cadena et al., 2010). A receptor fragment floating free in the blood works as a decoy: it traps those signals, and so blocks them, before they reach the receptors on muscle (Reichel et al., 2025). Because the activin type IIB receptor catches several signals, not one, the decoy catches several too — in binding experiments with a closely related soluble receptor-Fc protein made by the same company, myostatin (GDF-8) and GDF-11 bound about as tightly as activin A, while BMP-2 and BMP-7 bound at least 100-fold more weakly (Sako et al., 2010). Acceleron’s own papers describe the resulting drug as blocking “multiple negative regulators” of muscle rather than myostatin alone (Cadena et al., 2010).

The company history is short and dated. Acceleron licensed rights outside North America to Shire on September 8, 2010 for a non-refundable $45.0 million up front, with the two companies sharing the cost of developing ACE-031 in Duchenne muscular dystrophy. FDA placed the program on clinical hold on February 8, 2011. In April 2013 the companies decided not to take it further, Shire’s collaboration ended on June 30, 2013, and Acceleron wrote that it had “no plans to continue the development of ACE-031”, the risk-benefit profile being “not appropriate for the intended patient population, boys aged four and older” (Acceleron Form S-1, 2013). The Muscular Dystrophy Association, which had awarded Acceleron $1.5 million in January 2011 for the Duchenne work, published the companies’ April 21, 2011 statement and their May 2, 2013 announcement that the program would not restart (Muscular Dystrophy Association, 2013). The trial registrations today name the sponsor as Acceleron Pharma, a wholly owned subsidiary of Merck & Co. (ClinicalTrials.gov).

The published record is thin and easy to count. PubMed returns 12 records for “ACE-031” (October 4, 2026): the two human trials, three papers on the protein in animals (one of them the preprint and the journal version of the same marmoset study), two rat studies that used it as a tool to grow neck muscles, one analysis of products sold under its name, and four reviews or digests that mention it in passing. Europe PMC adds no study of the compound itself that PubMed misses (searched October 4, 2026). One of the rat papers describes ACE-031 as “a myostatin-specific inhibitor approved for clinical use in 2016” (Li et al., 2022); no regulatory record supports that, and Drugs@FDA holds no application for it (openFDA, read October 4, 2026).

Mechanism of Action

The binding work below comes from purified proteins and cells, the muscle findings from mice, rats and marmosets, and the human measurements from two trials. Most of it was done by the company that owned the molecule or by its former staff (Sako et al., 2010; Cadena et al., 2010; Cadena et al., 2026).

• Activin receptor type IIB (ActRIIB, gene ACVR2B), copied and set loose — The drug is the receptor’s extracellular region, residues 20–134 of the human precursor, fused through a three-glycine linker to the Fc tail of human IgG1 and paired into a dimer (WHO INN List 108, 2012; FDA substance registry). Its measured stay in the blood is long for an injected protein: a mean half-life of 10–15 days after one dose in healthy postmenopausal women, with exposure rising in proportion to dose (Attie et al., 2013).
• Myostatin (GDF-8), GDF-11 and activin A are what it catches — In kinetic experiments on a soluble ActRIIB-Fc chimera, GDF-8 and GDF-11 bound the extracellular domain with affinities comparable to activin A, a known high-affinity ligand, while BMP-2 and BMP-7 were at least 100-fold weaker; the authors, Acceleron scientists, also showed that the C-terminal end of the extracellular domain is needed to keep the chimera active (Sako et al., 2010). KEGG records the drug’s target as myostatin and its efficacy as myostatin inhibition (KEGG DRUG D10347).
• Blocking more than myostatin also hits BMP9 — the proposed reason for the bleeding — Cadena and colleagues write that the epistaxis and telangiectasias that stopped the Duchenne trial “were likely due to inhibition of BMP9, a ligand critical for vascular remodeling” (Cadena et al., 2026). The supporting work is in mice and used antibodies, not ACE-031: blocking BMP9 and BMP10 in newborn mice reproduced the vascular malformations of hereditary haemorrhagic telangiectasia in the retina (Ruiz et al., 2016). The same paper notes that a newer ligand trap, KER-065, shown to have 400-fold lower inhibitory activity against BMP9, had no epistaxis or telangiectasia reported in its Phase 1 in healthy volunteers, citing a 2025 meeting abstract (Cadena et al., 2026).
• Growth by thicker fibres, not more of them, and no fibre-type shift — In mice, four weeks of ACE-031 left the number of soleus fibres and the split between type I and type II fibres unchanged while mean fibre cross-sectional area rose 22% (type I) and 28% (type II); in the plantaris it rose 57% (Cadena et al., 2010). In marmosets after 14 weeks, biceps type II fibres were 20% larger and type I fibres 34% larger, and type I fibres made up 16% of the muscle in treated and untreated animals alike (Cadena et al., 2026). Myostatin-deficient mice, by contrast, shift towards fast fibres, which the authors read as a developmental effect rather than a drug effect (Cadena et al., 2026).
• Species differences the developers themselves flag — Cadena and colleagues note that circulating activin A in monkeys and people is reported 3–4 times higher than in mice and rats, and that a myostatin antibody needed 20 times the dose in monkeys to match the muscle gain it produced in mice; they use this to argue that drugs blocking myostatin alone, which worked in mice, are less likely to work in people, and that broader traps such as ACE-031 may do better in primates (Cadena et al., 2026). Reviews of the class report from the clinical side that no randomized trial in muscular dystrophy has shown functional improvement (Wagner, 2020; Rybalka et al., 2020).

What the Research Shows

These are the animal results. The two human trials are in the next section.

• Mice, four weeks (Cadena et al., 2010) — Eight-week-old male C57BL/6 mice, 5 per group, were dosed with 10 mg/kg twice a week for 28 days. Mean body weight ended 16% above the buffer-treated group by day 25; the wet weights of four hindlimb muscles were 26% to 46% greater (P < 0.05); fibre numbers did not change. Myosin heavy-chain protein proportions were unchanged in the soleus and plantaris, though plantaris transcripts for MHC I and IIa fell. Every experiment was “conceived, designed, performed, and analyzed by full-time Acceleron Pharma employees” (Cadena et al., 2010).
• Marmosets, 14 weeks — the only published primate study (Cadena et al., 2026) — Twelve adult common marmosets, randomized 8 to 3.0 mg/kg weekly under the skin and 4 to buffer. Lean body mass measured by quantitative magnetic resonance was higher than baseline from week 2 onward in the treated animals and flat in the controls; arm lean mass by DXA was higher than controls (p = 0.0225), while total body lean mass was not. Biceps fibres were larger, and specific twitch and specific tetanic force of the extensor digitorum longus were greater than controls — but absolute twitch and absolute tetanic force were not significantly different, a point the paper’s own abstract and discussion state more broadly than its results. Fat mass did not change, and serum chemistry stayed in range.
• Rats, into one muscle at a time (Li et al., 2022; Yang et al., 2023) — One anatomy group at Dalian Medical University used ACE-031 as a tool rather than as a candidate drug, in two papers that share eight authors. In the first, 5 mg/kg was injected weekly for 16 weeks into the small muscles at the back of 12 rats’ skulls, and into one calf muscle as an internal control, against saline in 12 other rats: neck-muscle fibre cross-sections were about 30% larger, the injected calf muscle about 20% heavier than the untreated leg’s, and its contraction force about 25% higher than the saline rats’; body weight did not differ significantly (Li et al., 2022). In the second, a single injection of 20 µl in all, at 50 ng/µl, went into the same neck muscles of 13 rats and was read out two weeks later (Yang et al., 2023). The purpose was cerebrospinal-fluid mechanics: the enlarged neck muscles raised intracranial pressure (Li et al., 2022) and the rate of cerebrospinal-fluid secretion, 0.935 against 0.711 µL/min in untouched rats (Yang et al., 2023). Both papers bought their ACE-031 from commercial reagent suppliers and report no test of what it contained (Li et al., 2022; Yang et al., 2023).
• Rats given a black-market product (Reichel et al., 2025) — Thirty Lewis rats got a single 10 mg/kg dose under the skin of a product sold as ACE-031, to see how long it could be detected: it was found in the serum of all rats at 24 hours, most at 48 hours and none at 7 days, and never in urine. The authors state plainly that giving black-market products to people was “not ethically justifiable”, which is why the study used rats.
• The mouse version, RAP-031, is a different molecule — Much of the early literature used ActRIIB fused to a mouse antibody tail, not ACE-031. In mice it raised lean mass, grip strength and contractile force and cut fat after 4 to 10 weeks (Akpan et al., 2009); it delayed weakness and increased grip strength in a model of amyotrophic lateral sclerosis without improving survival (Morrison et al., 2009); and in mdx mice, a model of Duchenne muscular dystrophy, 10 mg/kg for 12 weeks raised body weight 27% and lean mass 33% and lowered circulating creatine kinase (Pistilli et al., 2011). These results are about the mouse analog.

Human Data

Published: two randomized, double-blind, placebo-controlled trials, both sponsored by the developer. Registered with no results published: a multiple-dose Phase 1 in 70 healthy women and an open-label extension in 11 boys. Four registrations in all, the last of them finished in June 2011, and none recruiting or active since (ClinicalTrials.gov, searched October 4, 2026).

• Phase 1, single dose, 48 women (Attie et al., 2013) — Healthy postmenopausal women aged 45 to 75 at one centre were randomized 3 to 1 to a single dose of ACE-031 under the skin, from 0.02 to 3 mg/kg, or to placebo; the registration describes cohorts of 8, six on drug and two on placebo (NCT00755638). Exposure rose in line with dose and the mean half-life was 10–15 days. In the 3 mg/kg group, mean total body lean mass was 3.3% higher at day 29 by DXA (P = 0.03) and thigh muscle volume 5.1% higher by MRI (P = 0.03). Changes in serum markers of bone and fat metabolism were statistically significant, which the authors read as effects beyond muscle. The abstract names injection-site redness among the adverse events and calls the drug “generally well-tolerated” (Attie et al., 2013); the full report was not available for this page.
• Phase 1, multiple dose, 70 women — never published (NCT00952887) — The same population got either 2 or 3 doses over a month, or 7 doses over three months. It completed in February 2011. No results are posted and none have been published (PubMed and Europe PMC, searched October 4, 2026). This is the study in which repeated dosing in healthy adults was first measured, and its results are not public.
• Phase 2, 24 boys with Duchenne muscular dystrophy (Campbell et al., 2017) — A randomized, double-blind, placebo-controlled ascending-dose trial at Canadian sites: 18 boys on ACE-031 and 6 on placebo, all able to walk 10 metres in under 12 seconds and all on corticosteroids for at least a year at a stable dose, treated for 12 weeks and then followed for 12 weeks more (NCT01099761). The primary measure was safety. Cohort 1 took 0.5 mg/kg every 4 weeks and cohort 2 took 1.0 mg/kg every 2 weeks; a planned 2.5 mg/kg cohort was never enrolled because the trial was stopped. Lean body mass rose 3.6% and 4.1% against 2.6% on placebo, and lumbar-spine bone density 1.6% and 4.4% against 0.3%. The posted results give a p value for each arm on its own, not against placebo: lean mass p = 0.023 and p = 0.012 on the two doses and p = 0.435 on placebo; spine density p = 0.039 on the higher dose (NCT01099761). Six-minute walking distance changed by +43.8 m and +2.5 m on the two doses against +5.2 m on placebo in boys under 10, and by +4.5 m and −3.2 m against −47.6 m in boys 10 and over, with standard deviations of 23.6 to 61.5 m (NCT01099761); knee extension and knee flexion scores on hand-held myometry fell in all three groups. The published report calls the changes trends — for lean mass, fat mass, bone density and the walk test — and states that the walking difference was not statistically significant; it records no serious or severe adverse events (Campbell et al., 2017). A 2020 review counts the lean-mass rise in this trial as a statistically significant increase of under 5% (Rybalka et al., 2020).
• Why that trial stopped — “The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias” (Campbell et al., 2017). The posted results give the numbers: nosebleeds in 1 of 9 boys on the lower dose and 5 of 9 on the higher, telangiectasias in none and 5 of 9, against none of 6 on placebo; injection-site redness in 3 of 9, 6 of 9 and 3 of 6; headache in 1, 3 and 1. No serious adverse events in any arm. The registration’s reason for termination reads “Based on preliminary safety data” (NCT01099761).
• The extension, terminated (NCT01239758) — Eleven boys from the main trial continued open-label at their cohort’s dose — 0.5 mg/kg every 4 weeks or up to 1.0 mg/kg every 2 weeks — for a planned 24 weeks; the registration’s third arm, up to 2.5 mg/kg every 4 weeks, was the extension of the main trial’s cohort 3, which never enrolled (NCT01239758; NCT01099761). It was terminated in May 2011 “based on preliminary safety data”, and no results were posted or published.
• What the companies said at the time — Acceleron and Shire stated on April 21, 2011 that during trials “in healthy adults and in DMD boys, some participants experienced minor nosebleeds, gum bleeding, and/or small dilated blood vessels within the skin”, that these “all resolved fully upon discontinuation of treatment”, and that after review with FDA and Health Canada the Duchenne trial was terminated and the extension suspended; they said then that they intended to start new studies with added safety monitoring (Muscular Dystrophy Association, 2013). FDA’s clinical hold is dated February 8, 2011 (Acceleron Form S-1, 2013). Two years of animal toxicology followed, and on May 2, 2013, the day the companies announced the program would not restart, their clinical leads wrote to MDA that “the findings from these studies do not support further development” (Muscular Dystrophy Association, 2013).
• The class, not just this molecule — Randomized, double-blinded, placebo-controlled trials of myostatin inhibitors in both childhood and adult muscular dystrophies have not demonstrated functional improvement (Wagner, 2020). A second review notes that ACE-031 and three other inhibitors produced “mild (generally < 5%), yet statistically significant increases in muscle/lean mass” in boys with Duchenne, while none of the four showed the matching gain in strength and each missed its functional endpoints, and looks for the reasons both in the biology (corticosteroid co-treatment, scarred muscle) and in the trials’ choice of outcome measures and patient stratification (Rybalka et al., 2020). ACE-031 is the activin-receptor-decoy entry in that list.

The evidence meter on the ACE-031 card reads “Controlled trials”: it counts published human data on ACE-031 itself for the use on its tag, muscle, and two randomized placebo-controlled trials measured exactly that. Controlled is not the same as successful. The significant human results in healthy women are a 3.3% lean-mass gain and a 5.1% thigh-muscle gain 29 days after one 3 mg/kg dose (Attie et al., 2013); the trial in boys who needed the muscle was stopped at its second dose level and reported trends rather than a measured benefit (Campbell et al., 2017); and nothing has been published about the molecule in people since 2017.

Reconstitution & Storage

No label exists, because no health authority has approved ACE-031. The trials gave it as an injection under the skin; the registrations record the doses and the schedules but not the vial strength, the diluent or the storage conditions (NCT00755638; NCT01099761). Nothing published for this page gives a shelf life.

• What the trials used — Subcutaneous injections, single or every 2 to 4 weeks, at 0.02–3 mg/kg (healthy women) and 0.5–1.0 mg/kg (boys with Duchenne muscular dystrophy) (Attie et al., 2013; Campbell et al., 2017). Marmosets got weekly injections between the shoulder blades of protein purified on a protein A column and dialysed into Tris-buffered saline (Cadena et al., 2026).
• What is sold — One seller listing read for this page describes 1 mg of lyophilised powder a vial, labelled for research use only; it names no route. The 14 products the 2025 analysis bought in the UK, Europe, China and the USA were all marked “not for human consumption” or “for research purposes only” (Reichel et al., 2025).
• What is in it — Not ACE-031. Twelve of those 14 products held the full-length activin receptor type IIB, which is a transmembrane protein, not the receptor-Fc fusion; the enzyme IdeS, which cuts antibodies below the hinge and releases the Fc tail, could not cut them. Eleven of the twelve carried His-tags and all were impure, with many other proteins on the gel, and their apparent mass matched the unglycosylated receptor, pointing to bacterial rather than mammalian production (Reichel et al., 2025).
• Protein, not peptide — ACE-031 is a glycosylated two-chain protein of about 77,500 Da with seven internal disulfide bridges per chain and two bridges holding the chains together (WHO INN List 108, 2012; FDA substance registry). No published study has measured what handling outside a laboratory does to it.

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Side Effects & Risks

• What stopped the Duchenne trial — Nosebleeds and telangiectasias, small dilated vessels near the skin surface. On 1.0 mg/kg every 2 weeks, 5 of 9 boys had nosebleeds and 5 of 9 had telangiectasias; on 0.5 mg/kg every 4 weeks, 1 of 9 had a nosebleed and none had telangiectasias; none of the 6 boys on placebo had either (NCT01099761). The trial was terminated after that second dose level (Campbell et al., 2017).
• Severity, as recorded — No serious or severe adverse events were reported in the trial, in any arm (Campbell et al., 2017; NCT01099761), and the companies said the bleeding events and dilated vessels “all resolved fully upon discontinuation of treatment” and were not by themselves considered a serious safety concern — but that they needed to be understood before dosing continued, and FDA and Health Canada reviewed the data (Muscular Dystrophy Association, 2013).
• In healthy adults — The published single-dose study lists injection-site redness among its adverse events and calls the drug generally well tolerated (Attie et al., 2013). The companies’ own statement says participants in the healthy-adult trials also had minor nosebleeds, gum bleeding or small dilated skin vessels (Muscular Dystrophy Association, 2013); the multiple-dose study in 70 healthy women that would carry those data has never been published (NCT00952887).
• Why the vessels: a proposal, not a proven mechanism — Cadena and colleagues attribute the bleeding events to inhibition of BMP9, a signal needed for blood-vessel maintenance that this decoy also traps (Cadena et al., 2026). In newborn mice, blocking BMP9 and BMP10 with antibodies produced the vascular malformations of hereditary haemorrhagic telangiectasia (Ruiz et al., 2016). That work used antibodies in mice, not ACE-031 in people.
• Animal toxicology decided the program — After the hold, Acceleron and Shire ran further non-clinical and toxicology studies and concluded that the risk-benefit profile “was not appropriate for the intended patient population, boys aged four and older”; the findings themselves have not been published (Acceleron Form S-1, 2013; Muscular Dystrophy Association, 2013).
• A signal from the analog: testes in mice — A soluble activin type IIB ligand trap, not ACE-031, given to young male mice (10 mg/kg into the abdomen twice a week from day 17 to day 35 of life) produced muscle growth that faded and testicular changes that did not: smaller testes and changes in sperm quantity and quality persisting after dosing ended, with gene-expression abnormalities widening over time (Vaughan et al., 2021). That is a developing testis, and a different molecule. No ACE-031 trial measured testicular or sperm effects: the trials enrolled postmenopausal women and boys (NCT00755638; NCT00952887; NCT01099761).
• What has not been tested — No published trial gave ACE-031 to men, to athletes, or for longer than 12 weeks; the 24-week extension’s results were never published (NCT01239758). No drug-interaction study, no pregnancy data and no published toxicology turned up for it (PubMed and Europe PMC, searched October 4, 2026). Nothing has been published about it in people since 2017.
• WADA — Named on the 2026 Prohibited List. Section S4.3, agents preventing activin receptor IIB activation, lists “Decoy activin receptors (e.g. ACE-031)” among activin receptor IIB competitors, prohibited at all times, in and out of competition; S4.3 substances are non-Specified Substances (World Anti-Doping Agency, 2026). Laboratory methods for finding activin-receptor-Fc proteins in blood and urine are published and validated (Reichel et al., 2025; Sakellariou et al., 2025).

Bloodwork & Monitoring

No monitoring guidance for ACE-031 has been published outside the trials, and no label exists to set one. The trials measured these:

• Body composition and muscle imaging — Total body lean mass by DXA and thigh muscle volume by MRI in healthy women (Attie et al., 2013); lean body mass and lumbar-spine bone mineral density by DXA in the Duchenne trial (NCT01099761).
• Function — The six-minute walk test, a timed 10-metre walk or run, a four-stair climb, the Gower manoeuvre, hand-held myometry and fixed-system strength testing, and three breathing measures: forced vital capacity and maximum inspiratory and expiratory pressure (NCT01099761).
• Safety laboratory values — Clinical laboratory tests judged for treatment-emergent abnormalities: none in the Duchenne trial was judged at least possibly drug-related, in any arm (NCT01099761). The marmoset study tracked serum chemistry and blood counts at baseline and weeks 1, 4 and 8 (Cadena et al., 2026).
• Bone and fat markers — Serum markers of bone and fat metabolism changed significantly after a single dose in healthy women; the paper reports the direction as favourable without naming a monitoring use (Attie et al., 2013).
• What anti-doping laboratories look for — Not monitoring, but it is what exists: immunoaffinity purification followed by gel electrophoresis and immunoblotting detects activin-receptor products in serum and urine down to about 1 ng/mL in rat serum (Reichel et al., 2025), and a validated mass-spectrometry method covers nine activin-pathway inhibitors at 10–50 ng/mL (Sakellariou et al., 2025).
• Which tests fit a given person — A question for a licensed healthcare provider. This page can’t answer it.

Commonly Stacked With

ACE-031 has been given alongside one thing in a published trial: corticosteroids, which every boy in the Phase 2 had taken for at least a year and at a stable dose for at least six months before the first injection, so the trial measured ACE-031 added to steroid treatment rather than on its own (NCT01099761; Campbell et al., 2017). No study has tested ACE-031 with any other compound on this site, and no published document shows people combining it (PubMed and Europe PMC, searched October 4, 2026).

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Legal Status

Related Compounds

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Next Steps

References

1. FDA. Global Substance Registration System: Ramatercept, UNII 42HQC6QLEK (names ACE-031 and ramatercept; INN and USAN; USAN code YY-125; CAS 1169766-01-1; two identical 343-amino-acid subunits; N-glycosylation sites 23, 46 and 193 on each; calculated average molecular weight 77,500 Da). gsrs.ncats.nih.gov. Read October 4, 2026.
2. World Health Organization. International Nonproprietary Names for Pharmaceutical Substances: Proposed INN List 108. WHO Drug Information. 2012;26(4):440. Ramatercept: “Homo sapiens ACVR2B precursor fragment 20-134 (1-115) -triglycyl (116-118) -Homo sapiens IGHG1*03 H-CH2-CH3 fragment … (119-343); dimer (122-122’:125-125’)-bisdisulfide”. cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl108.pdf. Read October 4, 2026.
3. KEGG DRUG. Ramatercept (USAN/INN), entry D10347: 343-amino-acid sequence, formula C3418H5188N928O1062S38, molecular weight 77,489.89; efficacy “myostatin inhibitor”; target MSTN. rest.kegg.jp/get/dr:D10347. Read October 4, 2026.
4. Sako D, Grinberg AV, Liu J, Davies MV, et al. Characterization of the ligand binding functionality of the extracellular domain of activin receptor type IIb. J Biol Chem. 2010;285(27):21037-21048. PMID: 20385559. DOI: 10.1074/jbc.M110.114959.
5. Cadena SM, Tomkinson KN, Monnell TE, Spaits MS, et al. Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type. J Appl Physiol (1985). 2010;109(3):635-642. PMID: 20466801. DOI: 10.1152/japplphysiol.00866.2009.
6. Attie KM, Borgstein NG, Yang Y, Condon CH, et al. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013;47(3):416-423. PMID: 23169607. DOI: 10.1002/mus.23539.
7. Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, et al. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle Nerve. 2017;55(4):458-464. PMID: 27462804. DOI: 10.1002/mus.25268.
8. Cadena SM, Bogdanovich S, Khurana TS, Pullen A, et al. ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus). PLoS One. 2026;21(2):e0342666. PMID: 41686840. DOI: 10.1371/journal.pone.0342666. (Full text and competing-interests statement read at PMC12904423, October 4, 2026.)
9. Reichel C, Filip T, Gmeiner G, Thevis M. Gel Electrophoretic Detection of Black Market ACE-031. Drug Test Anal. 2025;17(10):1934-1946. PMID: 40312924. DOI: 10.1002/dta.3898. (Full text read at PMC12489275, October 4, 2026.)
10. Li C, Yue C, Liu ZC, Gong J, et al. The relationship between myodural bridges, hyperplasia of the suboccipital musculature, and intracranial pressure. PLoS One. 2022;17(9):e0273193. PMID: 36054096. DOI: 10.1371/journal.pone.0273193.
11. Yang H, Wei XS, Gong J, Du XM, et al. The relationship between myodural bridge, atrophy and hyperplasia of the suboccipital musculature, and cerebrospinal fluid dynamics. Sci Rep. 2023;13(1):18882. PMID: 37919345. DOI: 10.1038/s41598-023-45820-x.
12. Akpan I, Goncalves MD, Dhir R, Yin X, et al. The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity. Int J Obes (Lond). 2009;33(11):1265-1273. PMID: 19668253. DOI: 10.1038/ijo.2009.162.
13. Morrison BM, Lachey JL, Warsing LC, Ting BL, et al. A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2009;217(2):258-268. PMID: 19285073. DOI: 10.1016/j.expneurol.2009.02.017.
14. Pistilli EE, Bogdanovich S, Goncalves MD, Ahima RS, et al. Targeting the activin type IIB receptor to improve muscle mass and function in the mdx mouse model of Duchenne muscular dystrophy. Am J Pathol. 2011;178(3):1287-1297. PMID: 21356379. DOI: 10.1016/j.ajpath.2010.11.071.
15. Vaughan D, Mitchell R, Kretz O, Chambers D, et al. A muscle growth-promoting treatment based on the attenuation of activin/myostatin signalling results in long-term testicular abnormalities. Dis Model Mech. 2021;14(2):dmm047555. PMID: 33408083. DOI: 10.1242/dmm.047555.
16. Ruiz S, Zhao H, Chandakkar P, Chatterjee PK, et al. A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10. Sci Rep. 2016;6:37366. PMID: 27874028. DOI: 10.1038/srep37366.
17. Wagner KR. The elusive promise of myostatin inhibition for muscular dystrophy. Curr Opin Neurol. 2020;33(5):621-628. PMID: 32773450. DOI: 10.1097/WCO.0000000000000853.
18. Rybalka E, Timpani CA, Debruin DA, Bagaric RM, et al. The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle. Cells. 2020;9(12):2657. PMID: 33322031. DOI: 10.3390/cells9122657.
19. Sakellariou P, Walpurgis K, Thomas A, Marchand A, et al. Combined detection of inhibitors of the activin receptor signaling pathways (IASPs) by means of LC-HRMS/MS for human doping control. Sci Rep. 2025;15(1):19887. PMID: 40481031. DOI: 10.1038/s41598-025-03562-y.
20. Thevis M, Schänzer W. Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis - Potential implications for sports drug testing programs. Rapid Commun Mass Spectrom. 2016;30(5):635-651. PMID: 26842585. DOI: 10.1002/rcm.7470.
21. ClinicalTrials.gov. Registrations of ACE-031 (ActRIIB-IgG1), sponsor Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc.: NCT00755638 (Phase 1, single ascending dose, 48 healthy postmenopausal women, completed July 2009), NCT00952887 (Phase 1, multiple ascending dose, 70 healthy postmenopausal women, completed February 2011, no results posted), NCT01099761 (Phase 2 in Duchenne muscular dystrophy, 24 enrolled, terminated June 2011 “Based on preliminary safety data”, results posted October 2016) and NCT01239758 (open-label extension, 11 enrolled, terminated May 2011, no results posted). clinicaltrials.gov, API v2. Read October 4, 2026.
22. Acceleron Pharma Inc. Registration statement (Form S-1), filed August 7, 2013: the September 8, 2010 license and collaboration agreement with Shire AG and its $45.0 million up-front payment; “On February 8, 2011, the FDA placed ACE-031 on clinical hold”; the April 2013 decision not to advance ACE-031 and the termination of the Shire collaboration effective June 30, 2013; “we currently have no plans to continue the development of ACE-031”; and the risk-benefit profile judged “not appropriate for the intended patient population, boys aged four and older”. sec.gov/Archives/edgar/data/1280600/000104746913008148/a2216187zs-1.htm. Read October 4, 2026.
23. Muscular Dystrophy Association. UPDATE: ACE-031 Clinical Trials in Duchenne MD. Quest, published May 3, 2011, updated May 2, 2013: the companies’ April 21, 2011 joint statement (“minor nosebleeds, gum bleeding, and/or small dilated blood vessels within the skin”, “all resolved fully upon discontinuation of treatment”, termination of study A031-03 and suspension of A031-06 after review with FDA and Health Canada), the May 2, 2013 announcement that the program would not restart, the quoted May 2, 2013 communication (“the findings from these studies do not support further development”) and MDA’s January 2011 award of $1.5 million to Acceleron. mda.org. Read October 4, 2026.
24. FDA. Drugs@FDA through openFDA (api.fda.gov/drug/drugsfda.json): searches for “ACE-031” and “ramatercept”, October 4, 2026 — no applications.
25. US Code of Federal Regulations. 21 CFR 216.23, bulk drug substances that can be used to compound under section 503A, and 21 CFR 216.24, drug products withdrawn or removed from the market. ecfr.gov (version of October 1, 2026). Read October 4, 2026 — neither lists ACE-031 or ramatercept.
26. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated May 14, 2026. fda.gov/media/94155/download.
27. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated March 21, 2025. fda.gov/media/94164/download.
28. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S4.3, Agents preventing activin receptor IIB activation: “Activin receptor IIB competitors such as: … Decoy activin receptors (e.g. ACE-031)”; classes S4.3 and S4.4 are non-Specified Substances. wada-ama.org.
29. Searches of October 4, 2026: PubMed, “ACE-031” and “ACE031” (12 records each; 2 human trials, 3 animal papers on the protein, 2 rat studies using it as a tool, 1 analysis of marketed products, 4 reviews or digests) and “ramatercept” (1 record); PubMed, ACE-031 with exercise, resistance training, testosterone, growth hormone, IGF-1, corticosteroid, GLP-1 drugs and “combination” (no study of a combination); Europe PMC, “ACE-031 OR ACE031 OR ramatercept” (no study of the compound itself that PubMed lacks); ClinicalTrials.gov, “ACE-031”, “ACE031”, “ramatercept” and “ActRIIB-IgG1” (four ACE-031 registrations, none recruiting or active); openFDA Drugs@FDA (no application); greps of WADA’s 2026 List, FDA’s 503A and 503B category lists and 21 CFR 216 for ACE-031, ramatercept, activin, ActRII and myostatin; and one research-chemical listing describing 1 mg vials (seller not named).

Related Research

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