An Acceleron Pharma ActRIIB-Fc fusion protein (~110–115 kDa, not a peptide). Its only Phase 2 trial — in ambulatory boys with Duchenne muscular dystrophy — was halted in February 2011 for a vascular-leak phenotype. Program terminated 2013. StackTrax does not recommend ACE-031 use.
StackTrax doesn't endorse ACE-031 use. This guide exists because the compound is in gray-market circulation and users deserve the actual record. Three load-bearing facts.
Phase 2 was halted in February 2011 after the second cohort of DMD boys developed vascular adverse events — epistaxis (nosebleeds), telangiectasias (small dilated cutaneous vessels), gingival bleeding, and skin erythema. Acceleron and Shire formally announced trials would not resume on April 21, 2011. Program terminated 2013.
The vascular-leak signal is mechanistically explained, not stochastic. Off-target inhibition of BMP9/10 produces a phenotype indistinguishable from drug-induced hereditary hemorrhagic telangiectasia (HHT). This is intrinsic to the ActRIIB-Fc design.
Vendor "ACE-031" identity confidence is near zero. The legitimate molecule is a glycosylated dimeric Fc fusion produced in CHO cells — materially incompatible with the small-batch peptide CDMOs supplying the research-chemical market. What you receive in a vial labeled "ACE-031" almost certainly isn't the clinical molecule.
Existing peptide-knowledge content frames the trial halt as "minor nosebleeds and gum bleeding." That language understates the reality. Trials in DMD don't stop for trivial findings.
ACE-031 (also known as ramatercept) is a recombinant fusion protein, not a peptide. It's the extracellular ligand-binding domain of human activin receptor type IIB (ActRIIB / ACVR2B) — the receptor subunit through which myostatin and several activins initiate signaling — fused at its C-terminus to the hinge–CH2–CH3 region of human IgG1 Fc, produced as a glycosylated homodimer in mammalian (CHO) cells. Apparent molecular weight is ~110–115 kDa (each monomer ~55–58 kDa).
That's two to three orders of magnitude larger than a typical research peptide (BPC-157 is ~1.4 kDa). The disulfide architecture and glycosylation are required for activity and PK. Recombinant production at clinically relevant purity is meaningfully harder than producing a 30-residue peptide.
Originator was Acceleron Pharma, partnered with Shire plc (collaboration ended 2013). The Acceleron pipeline subsequently shifted: sotatercept (Winrevair, ACE-011) — ActRIIA-Fc — reached FDA approval March 26, 2024 for pulmonary arterial hypertension. The activin-trap class isn't categorically unsafe; ACE-031's specific failure mode reflects ActRIIB's specific promiscuity for BMP9/10.
ActRIIB is the principal type II receptor for myostatin (GDF-8). It also binds activin A, activin B, GDF-11, and — critically for the safety signal — has measurable affinity for several BMPs including BMP9 and BMP10.
The intended mechanism: ACE-031 (soluble ActRIIB-Fc) circulates in the bloodstream as a decoy, sequesters myostatin before it can engage cell-surface ActRIIB on muscle, reduces SMAD2/3 phosphorylation downstream, and derepresses muscle protein synthesis → muscle hypertrophy.
The off-target mechanism that broke the trial: the same ActRIIB-Fc trap also sequesters BMP9 and BMP10. These ligands signal through endothelial ALK1 with ENG (endoglin) as co-receptor, driving SMAD1/5/8 activation. This pathway is essential for vascular quiescence and capillary integrity. Loss-of-function mutations in ENG, ACVRL1 (ALK1), or SMAD4 cause hereditary hemorrhagic telangiectasia (HHT) — characterized by recurrent epistaxis, mucocutaneous telangiectasias, and arteriovenous malformations. ACE-031's pharmacologic depletion of BMP9/10 produces a phenotype indistinguishable from drug-induced HHT. The signal is predictable from the binding-promiscuity profile of ActRIIB-Fc — not a stochastic or idiosyncratic toxicity.
Acceleron's next-generation ligand traps explicitly addressed binding promiscuity. Luspatercept (Reblozyl) is an engineered ActRIIB-Fc shifted toward GDF11 over myostatin/activin A; FDA-approved for transfusion-dependent anemias. Sotatercept (Winrevair, ACE-011) uses ActRIIA, not ActRIIB; FDA-approved March 2024 for PAH. The class can succeed; ACE-031 specifically failed.
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Start Tracking FreePhase 1 SAD — Attie 2013. Attie KM, Borgstein NG, Yang Y, et al. Muscle Nerve 2013;47(3):416–423 (PMID 23169607). Randomized, double-blind, placebo-controlled, single ascending dose in 48 healthy postmenopausal women. Doses 0.02 to 3 mg/kg subcutaneously. At day 29, the 3 mg/kg cohort showed statistically significant increases in lean body mass (DXA) and thigh muscle volume (MRI). Bone-formation markers up; bone-resorption markers down. Adverse events at single dose were generally mild/moderate — the vascular bleeding signal wasn't dominant at single dose; it emerged with repeat dosing. Note: the existing StackTrax peptide-knowledge entry cited an incorrect DOI in Neuromuscular Disorders; the correct anchor is PMID 23169607 in Muscle & Nerve.
Phase 2 in DMD — Campbell 2017 (halted). Campbell C, McMillan HJ, Mah JK, et al. Muscle Nerve 2017;55(4):458–464 (PMID 27462804). Randomized, double-blind, placebo-controlled, multiple-dose, two sequential cohorts. Ambulatory boys with DMD, ages 4–11. SC dosing every 2–4 weeks for 24 weeks (C1: 0.5 mg/kg q4w; C2: 1.0 mg/kg q2w). Trial terminated early after the second cohort due to safety. Reported vascular AEs: epistaxis, telangiectasias, gingival bleeding, skin erythema. Trends toward lean-body-mass increase and stable/slightly improved 6MWT in the truncated dataset, not statistically conclusive.
The total human dataset: ~48 healthy postmenopausal women plus the truncated DMD cohort. No Phase 3, no extension study, no real-world registry, no long-term safety data.
Conflation with structurally and mechanistically different agents is widespread in gray-market literature.
| Molecule | What it is | Status |
|---|---|---|
| ACE-031 (this guide) | ActRIIB-Fc decoy receptor | Halted 2011; terminated 2013 |
| Sotatercept (Winrevair) | ActRIIA-Fc decoy receptor | FDA-approved March 2024 for PAH |
| Luspatercept (Reblozyl) | Engineered ActRIIB-Fc biased toward GDF11 | FDA-approved for anemias |
| Bimagrumab (BYM338) | Anti-ActRIIB monoclonal antibody | Failed Phase 2b/3 in sIBM 2016 |
| Follistatin / FS344 | Direct ligand-binding glycoprotein | Sarepta gene-therapy program ongoing; vendor protein unvalidated |
| Domagrozumab | Anti-myostatin antibody (Pfizer) | Failed Phase 2 in DMD |
| Stamulumab (MYO-029) | Anti-myostatin antibody (Wyeth) | Failed Phase 1/2 |
| Trevogrumab / Landogrozumab | Anti-myostatin antibodies | Halted |
| ACE-083 | Modified follistatin-Fc fusion (local) | Halted across FSHD and CMT 2019–2022 |
The big-pharma anti-myostatin class graveyard is the most underused calibration point for any "myostatin pathway" claim — multiple Phase 2/3 programs have produced lean-mass gains without functional improvement, with various safety signals.
Pre-filled with a typical ACE-031 (Ramatercept) setup. Edit any field — the draw updates live.
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ACE-031 is administered subcutaneously. As an IgG1-Fc-fused biologic recycled by the neonatal Fc receptor (FcRn), it has a long terminal half-life — on the order of weeks. Practical implications: any adverse event will persist for weeks regardless of dose discontinuation; steady-state accumulation over multi-dose dosing is non-trivial (the vascular signal in the Phase 2 DMD trial appeared at and after the second cohort's dosing as exposure accumulated, not after a single dose); and off-label "trial" dosing has no experimental basis for cycling, washout, or safety monitoring.
No published mass-balance, metabolism, or hepatic-impairment studies. No published interaction studies. No pediatric PK data outside the truncated DMD trial.
The previous framing of "minor nosebleeds and gum bleeding" understates the picture in three ways: the events were severe enough to halt a pediatric trial in a fatal disease (trials in DMD don't stop for trivial findings); they reflect a pharmacology-driven systemic vascular signal, not local irritation; and they cluster mechanistically with HHT, a known disease with documented serious sequelae including pulmonary and cerebral arteriovenous malformations. The trial duration was too short to know whether longer exposure would have produced these.
What was observed clinically: recurrent epistaxis (nosebleeds, the most readily-recognizable consumer-facing symptom); telangiectasias on face, hands, and oral mucosa; gingival bleeding spontaneously and with brushing; diffuse skin erythema and at injection sites.
Theoretical / unobserved-but-plausible additional risks for off-label use: reproductive (ActRIIB inhibition perturbs activin signaling in the gonadal axis — no human reproductive-tox data exist); cardiac (GDF-11 has been implicated in cardiac aging and is captured by ActRIIB-Fc traps; clinical relevance debated); tendon (aggressive muscle hypertrophy without commensurate tendon adaptation is a documented concern across the class in animal models); immunogenicity (anti-drug antibodies to a recombinant Fc fusion are routine; detailed ACE-031 immunogenicity data not in peer-reviewed literature).
The molecule described in this guide and the vial sold under the same name on research-chemical sites aren't necessarily the same thing.
The legitimate clinical molecule is a glycosylated dimeric Fc fusion produced in CHO cells, with disulfide-bonded structure and post-translational modifications required for activity and PK, ~110–115 kDa, materially incompatible with synthesis by the small-batch peptide CDMOs that supply the research-chemical market.
Vendor "ACE-031" is typically sold as a lyophilized vial in the 1–3 mg range at peptide-vendor pricing. Independent identity testing of vendor product isn't publicly published. Mass-spec, SDS-PAGE, and SEC profiles compatible with a ~115 kDa glycosylated Fc fusion aren't characteristic of what these vendors typically deliver.
Plausible vendor realities (none currently rule-out-able for any specific lot): empty / excipient-only vials; unrelated recombinant protein at low purity; an unrelated peptide labeled "ACE-031"; bacterial-expressed unglycosylated ActRIIB ECD without Fc (which would have neither the half-life nor the activity profile of the clinical molecule); rarely, a low-purity Fc fusion of indeterminate activity.
For ACE-031 specifically, vendor identity confidence should be treated as near zero by default. A user reporting "I tried ACE-031 and felt nothing" or "I tried it and got nosebleeds" has no way to know what was actually injected. Both outcomes are consistent with the gray-market identity-uncertainty problem and provide no information about the legitimate molecule.
If you've already used vendor "ACE-031": stop, document any nasal/oral/skin bleeding or erythema with photos and dates, see a physician (bring the Campbell 2017 paper, PMID 27462804), don't redose, and be aware the half-life is on the order of weeks — symptoms may persist after stopping.
ACE-031 (Ramatercept) is a research peptide not approved by the FDA for human use. It is sold only as a research chemical, and StackTrax does not endorse or facilitate personal use.
Quality varies enormously among research-chemical suppliers. At minimum, look for:
StackTrax’s preferred partner NextGen Peptides does not currently carry ACE-031 (Ramatercept)in their catalog, which is why you don’t see a direct purchase link here. Other major research-chemical suppliers carry it; we don’t specifically recommend one for this compound.
ACE-031 (also known as ramatercept) is a recombinant fusion protein, not a peptide. It is the extracellular ligand-binding domain of human activin receptor type IIB (ActRIIB / ACVR2B) fused at its C-terminus to the hinge-CH2-CH3 region of human IgG1 Fc, produced as a glycosylated homodimer in mammalian CHO cells. Apparent molecular weight is about 110 to 115 kDa, two to three orders of magnitude larger than a typical research peptide. Originator was Acceleron Pharma, partnered with Shire; the collaboration ended in 2013.
ActRIIB is the principal type II receptor for myostatin (GDF-8) and also binds activin A, activin B, GDF-11, and several BMPs including BMP9 and BMP10. The intended mechanism: ACE-031 circulates as a soluble decoy, sequesters myostatin before it can engage cell-surface ActRIIB on muscle, reduces SMAD2/3 phosphorylation, and derepresses muscle protein synthesis to drive hypertrophy. The off-target mechanism that broke the trial: the same trap also sequesters BMP9 and BMP10, which signal through endothelial ALK1 with endoglin to maintain vascular quiescence and capillary integrity.
The only Phase 2 trial, in ambulatory boys with Duchenne muscular dystrophy (NCT01099761, Campbell 2017 PMID 27462804), was halted in February 2011 after the second cohort developed vascular adverse events: epistaxis (nosebleeds), telangiectasias, gingival bleeding, and skin erythema. Acceleron and Shire formally announced trials would not resume on April 21, 2011, and the program was terminated in 2013. The vascular-leak signal is mechanistically explained, not stochastic: pharmacologic depletion of BMP9/10 produces a phenotype indistinguishable from drug-induced hereditary hemorrhagic telangiectasia (HHT). Trials in DMD don't stop for trivial findings.
Trial doses were 0.5 mg/kg every 4 weeks (cohort C1) and 1.0 mg/kg every 2 weeks (cohort C2) SC for 24 weeks in DMD boys; Phase 1 SAD in healthy postmenopausal women used 0.02 to 3 mg/kg SC. There is no validated community dose. As an IgG1-Fc-fused biologic recycled by FcRn, ACE-031 has a long terminal half-life on the order of weeks, so any adverse event persists for weeks regardless of discontinuation and off-label dosing has no experimental basis for cycling, washout, or safety monitoring. StackTrax does not endorse ACE-031 use.
Observed clinical adverse events were recurrent epistaxis, telangiectasias on face, hands, and oral mucosa, gingival bleeding, and diffuse skin erythema. Theoretical additional risks for off-label use include reproductive effects (ActRIIB inhibition perturbs activin signaling in the gonadal axis, no human reproductive-tox data exist), cardiac concerns from GDF-11 capture, tendon adaptation lagging muscle hypertrophy, and immunogenicity. Absolute contraindications include pregnancy, breastfeeding or planning pregnancy, personal or family history of HHT or AVMs or unexplained recurrent epistaxis, bleeding disorders, and concurrent anticoagulant or antiplatelet therapy. WADA prohibits myostatin pathway antagonists at all times under S4.
Sotatercept (Winrevair) uses ActRIIA rather than ActRIIB and was FDA-approved in March 2024 for pulmonary arterial hypertension. Luspatercept (Reblozyl) is an engineered ActRIIB-Fc shifted toward GDF11 over myostatin/activin A, FDA-approved for transfusion-dependent anemias. The activin-trap class isn't categorically unsafe; ACE-031's specific failure mode reflects ActRIIB's promiscuity for BMP9/10. Follistatin is a direct ligand-binding glycoprotein (different mechanism class). Bimagrumab, domagrozumab, stamulumab, trevogrumab, and landogrozumab are all antibody-based programs that failed or were halted, reflecting the broader anti-myostatin class graveyard.
Vendor identity confidence should be treated as near zero. The legitimate clinical molecule is a glycosylated dimeric Fc fusion produced in CHO cells with disulfide-bonded structure and post-translational modifications required for activity, around 110 to 115 kDa, materially incompatible with the small-batch peptide CDMOs that supply the research-chemical market. Vendor "ACE-031" is typically sold as a 1 to 3 mg lyophilized vial at peptide-vendor pricing. Plausible vendor realities include empty or excipient-only vials, unrelated recombinant protein at low purity, an unrelated peptide mislabeled, or bacterial-expressed unglycosylated ActRIIB without Fc. A user reporting they tried it and felt nothing, or got nosebleeds, has no way to know what was actually injected.
Disclaimer: This guide is for educational and informational purposes only and is not intended as medical advice, diagnosis, or treatment. The compounds discussed are not FDA approved for human use. Always consult a qualified healthcare provider before starting any new supplement or peptide protocol. StackTrax does not sell peptides or supplements directly — purchase links go to third-party vendors. StackTrax is not responsible for the products, quality, or business practices of any third-party vendor. This page contains affiliate links — StackTrax may earn a commission on purchases at no extra cost to you.
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StackTrax guides cover peptides and compounds that are not FDA-approved for the uses discussed. The dosing, reconstitution, and safety information is compiled from published research and community protocols for educational purposes only.
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