Reference/Soluble activin receptor type IIB-Fc fusion protein

ACE-031

Myostatin Inhibitor · Experimental Muscle Growth

Mechanistic

research use only

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.

Significant lean mass increases (up to 1.7% in 29 days) observed in Phase 1 trialsSimultaneous reduction in fat mass alongside muscle gainsLong half-life (12-15 days) allows infrequent dosingBroad TGF-beta ligand neutralization for robust anti-catabolic effects

4 citations·0 with human data·Updated 10 Aug 2026

Overview

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.

Evidence profilederived from 4 references

Mechanistic

Strongest design among the references on this page. Grade and effect size are separate facts and are never merged into one score.

Research indications

What the compound has been studied for, grouped by body system. Effect size is the reported magnitude where it was measured — not a recommendation.

Muscle Growth3

Muscle Hypertrophy

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

Large

Muscular Dystrophy

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.

Moderate

Muscle Wasting / Cachexia

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

Moderate

Body Composition2

Fat Loss

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

Moderate

Bone Density

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

Small

A large effect in a weak study and a small effect in a strong one are different things. Effect size is never evidence of use in people.

Quick factsreference only

Class: Soluble activin receptor type IIB-Fc fusion protein
Half-life: ~324 h
Typical dose: 0.5-3 mg/kg IV every 2 weeks (clinical research doses only)
Frequency: Every 2 weeks
Cycle length: Clinical trials used 4-12 week treatment periods
Storage: 2-8°C; protect from light. Not commercially available.

Molecular data

Type: Soluble activin receptor type IIB-Fc fusion protein
Half-life: 19440 min

Dosing reference

Doses reported in the literature and by suppliers. These are a record of what has been used in research — reference, never instruction.

Context	Route	Amount	Frequency
Phase 1 Research Protocol (Healthy Volunteers)	IV infusion	0.1-3 mg/kg	Single IV dose
Phase 2 Research Protocol (DMD)	IV or SubQ	0.5-2.5 mg/kg	Every 2 weeks

Interactions

Follistatin

Both inhibit myostatin through different mechanisms (ligand trapping vs. direct binding). Conceptually synergistic, but no clinical data on combination use.

synergistic

YK-11

Both target the myostatin pathway. YK-11 acts as a myostatin inhibitor through a different mechanism. Combined use could produce excessive pathway suppression with unpredictable effects.

monitor

Quality checklist

✓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
!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
×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

What to expect

Week 1-2Initial ligand trapping begins; circulating myostatin levels decrease. No overt physical changes expected yet.

Week 2-4Measurable lean mass increases detectable by DXA/MRI. Phase 1 data showed +1.7% lean mass by day 29. Possible onset of vascular side effects (nosebleeds).

Week 4-8Continued muscle accretion with repeated dosing. Fat mass reduction becomes more apparent. Monitor closely for telangiectasia and bleeding events.

Post-treatmentEffects diminish over several weeks as drug clears. Muscle gains may partially persist with continued resistance training.

Safety

Commonly reported5

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 and seek advice5

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

Contraindications5

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

FAQ

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

1
Myostatin inhibition in health and disease
Lee SJ · Annual Review of Cell and Developmental Biology · 2004
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.
reviewPubMed 15473835 ↗
2
A soluble activin receptor type IIB (ACE-031) increases lean body mass and muscle strength in healthy postmenopausal women
Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML · Journal of Clinical Endocrinology & Metabolism · 2013
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.
reviewPubMed 23539721 ↗
3
Pharmacokinetic, pharmacodynamic, and safety results from a first-in-human study of ACE-031, a novel activin receptor type IIB/Fc fusion protein
Bhatt RS, Goss A, Wilson DM, Borgstein NG, Sherman ML · Journal of Clinical Pharmacology · 2014
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.
reviewPubMed 24691811 ↗
4
A phase 2 trial of ACE-031, a soluble activin receptor type IIB, in boys with Duchenne muscular dystrophy
Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, Selby K, McClure T, Wilson DM, Sherman ML, Bhatt SA, Trachtenberg FL, Kunkel LM, Bhatt RS · Neuromuscular Disorders · 2017
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.
reviewPubMed 28131562 ↗