ACE-031 Overview, Dosing & Safety | Peptide Database

ACE-031 (ACVR2B-Fc)

Myostatin Inhibitor | Experimental Muscle Growth

Community Research

Join others researching ACE-031 — share findings, ask questions, and learn from real experiences

ACE-031 is a soluble form of the activin type IIB receptor (ActRIIB) fused to an IgG1 Fc domain. It functions as a decoy receptor, binding and neutralizing myostatin and other TGF-beta superfamily members that normally limit muscle growth. Originally developed by Acceleron Pharma for Duchenne muscular dystrophy (DMD), ACE-031 reached Phase 2 clinical trials before development was halted due to vascular side effects including nosebleeds and telangiectasia. In healthy volunteers, a single dose produced significant increases in lean mass and reductions in fat mass within 29 days.

ACE-031 acts as a ligand trap for members of the TGF-beta superfamily. By mimicking the extracellular domain of the ActRIIB receptor, it intercepts myostatin (GDF-8), activin A, activin B, and GDF-11 before they can bind cell-surface receptors and activate Smad2/3 signaling. Blocking this pathway removes the natural brake on muscle protein synthesis and satellite cell proliferation, resulting in rapid skeletal muscle hypertrophy. The Fc fusion domain extends circulating half-life through FcRn-mediated recycling and provides bivalent ligand binding.

Molecular Data

Research Indications

Phase 1 data showed statistically significant lean mass increases (average +1.7%) after a single IV dose in healthy postmenopausal women.

Phase 2 trial in DMD patients showed improvements in lean body mass and bone mineral density, but trial was halted due to vascular adverse events.

Preclinical models demonstrate robust prevention of muscle loss in disease states through myostatin pathway inhibition.

Phase 1 trial subjects showed concurrent fat mass reductions alongside lean mass gains, suggesting favorable nutrient partitioning.

DMD trial data showed increases in bone mineral density, consistent with known effects of ActRIIB pathway modulation on bone metabolism.

Dosing Protocols

Administered as an intravenous infusion in clinical trials. Research doses ranged from 0.1 to 3 mg/kg given every 2 weeks. This compound is not commercially available and has never been approved for any indication.

Phase 1 Research Protocol (Healthy Volunteers)

0.1-3 mg/kg

Single IV dose

IV infusion

Phase 2 Research Protocol (DMD)

0.5-2.5 mg/kg

Every 2 weeks

IV or SubQ

Interactions

What to Expect

Side Effects & Safety

Common Side Effects

Nosebleeds (epistaxis) - most frequently reported adverse event

Gum bleeding

Telangiectasia (dilated small blood vessels visible on skin)

Skin erythema (redness)

Minor injection site reactions

Stop Signs - Discontinue if:

Recurrent or severe nosebleeds

Development of new or worsening telangiectasia

Unexplained bleeding from any site

Signs of hereditary hemorrhagic telangiectasia-like syndrome

Severe skin reactions or widespread erythema

Contraindications

NEVER approved for human use - clinical development discontinued

History of bleeding disorders or vascular malformations

Concurrent anticoagulant or antiplatelet therapy

Known hypersensitivity to Fc fusion proteins

Pregnancy or breastfeeding

Quality Checklist

Good Signs

Manufactured under GMP conditions for clinical trials

Characterized by SDS-PAGE and mass spectrometry

Endotoxin-tested and sterility-verified

Stored at 2-8°C with documented cold chain

Warning Signs

Clinical development halted - not commercially manufactured

No legitimate commercial source exists

Any product sold as ACE-031 is of unknown origin and quality

Fusion protein structure is sensitive to degradation

Bad Signs

Vascular side effects led to trial discontinuation - nosebleeds and telangiectasia were dose-limiting

Broad ligand trapping may cause unintended effects beyond myostatin inhibition

Long-term safety profile completely unknown

Frequently Asked Questions

Why did ACE-031 development stop if it showed such impressive muscle gains?

ACE-031 was halted during Phase 2 clinical trials due to serious vascular side effects including recurrent nosebleeds, gum bleeding, and telangiectasia (dilated small blood vessels visible on skin). These dose-limiting adverse events suggested off-target effects on vascular homeostasis that outweighed the muscle-building benefits, making further development unsafe.

How much muscle can ACE-031 actually build in humans?

Phase 1 data in healthy postmenopausal women showed statistically significant lean mass increases (+1.7%) and thigh muscle volume increases (+5.1%) after a single IV dose within 29 days. However, development never progressed to Phase 3, so real-world efficacy at therapeutic doses and long-term safety remain unproven in larger populations.

Can I use ACE-031 as a research chemical if I can find it?

ACE-031 has never been approved for human use and clinical development was discontinued. Any product sold as ACE-031 is of unknown origin and quality. The compound is a complex fusion protein sensitive to degradation, making DIY sourcing extremely risky with high contamination likelihood.

Does ACE-031 work through a different mechanism than myostatin inhibitors like follistatin?

No. ACE-031 is a soluble activin receptor that acts as a ligand trap, while follistatin directly binds myostatin. Both ultimately inhibit myostatin signaling, but through different mechanisms. Theoretically combined use might be synergistic, but clinical data on combinations doesn't exist.

References

Single ascending-dose Phase 1 trial in 48 postmenopausal women. ACE-031 produced statistically significant increases in total body lean mass (+1.7%) and thigh muscle volume (+5.1%) by day 29, with concurrent decreases in fat mass and leptin.

Phase 2 study in 12 DMD boys showed increases in lean body mass and bone mineral density. Trial was halted due to safety concerns including epistaxis, telangiectasia, and erythema. Preliminary efficacy signals were observed but could not be fully evaluated.

ACE-031 demonstrated a half-life of approximately 12 days with dose-proportional pharmacokinetics. The compound suppressed circulating FSH levels, consistent with activin A neutralization, and showed a dose-dependent increase in lean mass biomarkers.

Comprehensive review establishing myostatin as a key negative regulator of skeletal muscle mass. Demonstrated that myostatin-null mice exhibit dramatic increases in muscle mass, providing the biological rationale for therapeutic myostatin inhibition strategies including soluble receptor approaches.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.