ACE-031
Myostatin-pathway inhibitor
A soluble activin receptor type-IIB fusion protein referenced in myostatin-pathway and muscle-research literature.
Also referenced as: Ramatercept, ACE031
Overview
ACE-031 (ramatercept) is an engineered soluble fusion protein consisting of a portion of the activin receptor type IIB (ActRIIB) extracellular domain fused to a human IgG Fc region. It was developed by Acceleron Pharma as an investigational myostatin-pathway agent.
At a glance
What ACE-031 does
ACE-031 is an engineered soluble decoy receptor rather than a peptide agonist: it fuses the extracellular ligand-binding domain of activin receptor type IIB (ActRIIB) to the Fc portion of a human IgG antibody. Its job is to intercept and neutralize circulating growth factors before they can reach the real ActRIIB receptors on muscle cells. Chief among these ligands is myostatin (GDF-8), the body's principal brake on skeletal-muscle growth, along with activins and several related TGF-beta superfamily members that also signal through ActRIIB.
By binding and sequestering myostatin and activins, ACE-031 blocks their engagement of ActRIIB and the downstream SMAD2/3 signaling that normally restrains muscle protein accumulation. Removing that brake tips the balance toward net muscle growth - hypertrophy of existing fibers and increased muscle mass and strength. Because it soaks up multiple ligands at once, its effect is generally larger than blocking myostatin alone, but that same broad ligand promiscuity is the source of its off-target effects.
Unlike many entries in this catalog, ACE-031 reached human testing. In healthy postmenopausal women a single dose increased lean/muscle mass, and it was studied in boys with Duchenne muscular dystrophy. However, clinical development was halted over safety signals tied to hitting non-myostatin ligands - nosebleeds, gum bleeding, and dilated blood vessels (telangiectasias) - consistent with effects on the vascular/BMP arm of the pathway. So the muscle-building action is real and human-confirmed, but the on-target-adjacent toxicity is the reason it is not an approved product.
Effects reported in research
- Acts as a soluble ActRIIB-Fc decoy that binds and sequesters myostatin (GDF-8), preventing it from activating ActRIIB (established mechanism).
- Also neutralizes activins and other ActRIIB ligands, giving a broader blockade than selective anti-myostatin agents (established mechanism).
- Blocks downstream SMAD2/3 signaling that normally restrains muscle protein accumulation, releasing the brake on growth (mechanistic).
- Increased lean/muscle mass after a single dose in healthy postmenopausal women (human phase 1 trial).
- Increased muscle mass and strength in animal models of muscle wasting and dystrophy (animal).
- Studied in boys with Duchenne muscular dystrophy as a muscle-preserving strategy (human trial, discontinued).
- Produced off-target vascular/bleeding effects - epistaxis (nosebleeds), gum bleeding, and telangiectasias - attributed to blockade of non-myostatin ligands, which halted its clinical development (human trial safety findings).
Effects listed reflect findings reported in the research literature — many in animal or in-vitro models. Listing an effect is not a claim of efficacy or a therapeutic indication in humans.
Mechanism of action
ACE-031 acts as a decoy receptor: its ActRIIB extracellular domain binds and sequesters ligands that normally signal through ActRIIB, including myostatin (GDF-8) and related TGF-beta superfamily members such as activins. By preventing these ligands from engaging cell-surface ActRIIB, it blocks the negative regulatory signaling that restrains muscle growth, which in studies was associated with increased muscle mass. It is a fusion protein rather than a small peptide.
Mechanistic description reflects published research-literature understanding. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
What it's studied for
Research contexts in which ACE-031 appears in the literature. Listing a research area is not a claim of efficacy or a therapeutic indication.
Key characteristics
- ActRIIB extracellular domain fused to an IgG Fc (a ligand-trap fusion protein).
- Sequesters myostatin and related ActRIIB ligands (decoy-receptor mechanism).
- Blocks negative regulation of muscle growth.
- Investigated for muscle-wasting conditions but not approved.
- A larger fusion protein rather than a synthetic peptide.
Reported research dosing reference only
Educational reference, not dosing guidance. The figures below summarize amounts reported in published research and research-community protocols, provided for educational and research context only. They are not medical advice, not a recommendation, and not instructions for human use. ACE-031 is a research compound.
In its Phase 1 program ACE-031 was administered as subcutaneous doses expressed per kilogram of body weight, reflecting its status as a biologic. These are historical clinical-trial reference figures, not human-use guidance.
- Phase 1 clinical reference: single subcutaneous doses reported around 1-3 mg/kg, with the 3 mg/kg dose producing the largest reported lean-mass and thigh-muscle-volume changes over ~29 days
These are reference figures for research context only, not dosing guidance for humans. Its long Fc-driven half-life underlies the multi-week dosing interval seen in trials.
How it compares
ACE-031 is a soluble ActRIIB-Fc decoy receptor that traps multiple ligands at the receptor level, differing from Follistatin, which binds myostatin/activin as a natural extracellular antagonist.
Commonly studied alongside
Compounds frequently researched together with ACE-031 in the literature. Cross-referenced for research context — not a usage or combination recommendation.
Compare and calculate
Side-by-side pages for the pairings the literature already documents for ACE-031, plus the unit-conversion reference for a reconstituted vial. Factual comparisons of documented characteristics — not a recommendation to combine or use any compound.
ACE-031 reconstitution calculator → Concentration, volume per measured amount and syringe units for a stated vial mass and diluent volume. A unit-conversion reference, not a dosing recommendation.
Handling & Stability
Lyophilized peptides are stored cold, protected from light, and reconstituted only at the time of intended in-vitro work.
- Avoid repeated freeze-thaw cycles
- Verify supplier lot and Certificate of Analysis
- Follow institutional lab-safety protocols
Analytical & COA Concepts
Reputable research suppliers publish a third-party Certificate of Analysis per batch. Key analytical concepts referenced in COAs include:
Category Context
ACE-031 sits in the Specialty & Research area of the PeptiDex library.
- Entry type: Research compound reference
- Specialty & Research category hub →
- Browse the full library →
- Glossary of terms →
Where researchers source ACE-031
For researchers studying ACE-031, third-party suppliers such as Practically Natty Peptides offer research-grade material, third-party tests every batch and provides Certificates of Analysis on request, and ship from the US.
PeptiDex does not maintain a direct supplier listing for this compound. The link above goes to a third-party research-supplier directory.
Frequently asked questions
What is ACE-031 and what class of molecule is it?
ACE-031 (also called ramatercept) is not a small peptide but a recombinant fusion protein: the extracellular domain of the human activin receptor type IIB (ActRIIB / ACVR2B) fused to the Fc portion of human IgG1. It functions as a soluble 'ligand trap' or decoy receptor. Its class is a myostatin/activin-pathway inhibitor.
How does ACE-031 work as a myostatin inhibitor?
As a soluble decoy receptor it circulates and binds TGF-beta superfamily ligands - most notably myostatin (GDF-8), but also activin A/B, GDF-11 and certain BMPs - before they can engage native membrane-bound ActRIIB. By sequestering these growth-inhibitory ligands, it is studied for effects on muscle mass and strength in preclinical models.
How does ACE-031 differ from follistatin-344?
Both target the myostatin/activin axis but by different means. ACE-031 is an ActRIIB-Fc decoy receptor that traps ligands in circulation, whereas follistatin-344 is a natural glycoprotein that directly binds and neutralizes myostatin and activin with high affinity. They are frequently discussed together in muscle-growth research as two distinct mechanisms of myostatin inhibition.
What happened in ACE-031's clinical development?
ACE-031 was developed by Acceleron Pharma (with Shire) and studied in a Phase 1/2 setting including Duchenne muscular dystrophy. Reported early data suggested increases in lean and muscle mass, but development was halted after non-muscle safety signals (including bleeding and vascular effects attributed to off-target BMP9/BMP10 inhibition). It is not an approved drug.
Why is ACE-031's large size relevant to research handling?
Because ACE-031 is a ~80 kDa glycosylated Fc-fusion protein rather than a sub-10 kDa peptide, it behaves like an antibody-type biologic: it has a long circulating half-life driven by Fc recycling and requires cold-chain handling. This distinguishes its stability and dosing-interval considerations sharply from small synthetic peptides.
Answers are educational summaries of research-literature context and do not constitute medical advice. See the Research Library, COA guide, and Storage & Handling guide for more.
References
Primary literature indexed in PubMed for ACE-031. Listing a study records that it exists and is indexed — it is not a claim of efficacy, a therapeutic indication, or an endorsement of its conclusions. Much of this literature is preclinical (in-vitro or animal-model).
- A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers
- Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial
- Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type
Each reference was checked against its PubMed record on 2026-07-28: the PMID resolves and the title, journal and year match. Where no indexed literature exists for a compound, PeptiDex says so rather than substituting a citation about a different molecule. See the editorial policy.