ACE-031 is a soluble decoy receptor: the extracellular ligand-binding domain of human activin receptor type IIB fused to the Fc region of human IgG1, expressed as a disulfide-linked homodimer. It works by intercepting myostatin and related TGF-β superfamily ligands in the extracellular space before they can reach the membrane-bound receptor. Developed by Acceleron Pharma and also catalogued as ActRIIB-Fc or ramatercept, it reached Phase 2 clinical study and was discontinued in 2013 — a history that is central to how the molecule should be read in the literature.
MyPeptide supplies ACE-031 as a lyophilized recombinant protein in a 1 mg vial within the IGF and muscle peptides range. Supplied for laboratory research only; not for human or veterinary use.
What is ACE-031?
ACE-031 is a fusion protein, not a peptide. Two components define it. The first is the extracellular domain of ActRIIB, one of two type II activin receptors that sit at the top of the SMAD2/3 signalling cascade in skeletal muscle. The second is the Fc fragment of human IgG1, a standard protein-engineering module that adds two properties at once: it drives dimerisation, giving the construct two ligand-binding arms, and it engages the neonatal Fc receptor recycling pathway, which extends circulating persistence from hours to days.
The result is a molecule with the binding specificity of a receptor and the pharmacokinetics of an antibody, without any signalling capacity of its own — the classic ligand-trap design. As a dimeric glycoprotein it runs well above 70 kDa on SDS-PAGE, which is a useful identity check in itself.
Origin and structure
The design follows directly from the genetics of the myostatin pathway. Myostatin (GDF-8) is a negative regulator of skeletal muscle mass; animals and humans carrying loss-of-function variants show pronounced muscle overgrowth. Because myostatin signals through ActRIIB, presenting an excess of soluble ActRIIB in the extracellular space competes ligand away from the membrane receptor.
The engineering detail that matters most is what else ActRIIB binds. Its natural ligand repertoire includes activin A and activin B, GDF-11 — a close myostatin homologue with roles in development — and several bone morphogenetic proteins, including BMP9 and BMP10. A soluble ActRIIB trap therefore removes more than myostatin from circulation, and later engineering work in this class has focused specifically on narrowing that promiscuity.
How ACE-031 is thought to work
The mechanism is competitive ligand sequestration upstream of the receptor. With ligand bound to the trap, ActRIIB on the myocyte surface is not engaged, the type I receptor (ALK4/ALK5) is not recruited and phosphorylated, and SMAD2/3 signalling into the nucleus falls. In muscle models this is reported to relieve transcriptional suppression of growth programmes and to shift the balance towards Akt/mTOR-associated protein synthesis signalling.
Two mechanistic consequences follow from the broad binding profile. First, effects on bone were reported alongside effects on muscle in preclinical work, consistent with activin and BMP involvement in bone remodelling. Second, and more consequentially, BMP9 and BMP10 signalling through ALK1 in vascular endothelium is a recognised regulator of vascular integrity — and the vascular findings that ended clinical development of ACE-031 are generally attributed in the literature to that arm rather than to the muscle pathway. For a researcher, this makes ACE-031 a broad-spectrum ActRIIB ligand trap rather than a myostatin-specific tool, and the distinction should be stated explicitly in any interpretation.
Compared with Follistatin-344, which binds the ligands themselves, and with GDF-8 / myostatin propeptide, which is the ligand's own natural inhibitor and is the most selective of the three, ACE-031 blocks the axis at the receptor interface. Choosing between them is a real experimental decision about where in the pathway the intervention should sit.
What the research has examined
Preclinical muscle and bone models
Rodent studies with soluble ActRIIB-Fc constructs reported substantial increases in lean mass and muscle fibre size, including in dystrophic and cachexia models, and separate studies reported increases in bone mineral density. These are the findings that motivated clinical development.
Phase 1 human pharmacology
A Phase 1 study in healthy postmenopausal volunteers reported increases in lean mass and changes in bone-formation and fat-mass markers after single administration, alongside pharmacokinetic data consistent with the Fc-extended half-life. This is the clearest published human evidence that the mechanism engages its target in people.
Duchenne muscular dystrophy studies and discontinuation
A Phase 2 programme in boys with Duchenne muscular dystrophy was halted in 2013. The reported reason was not lack of muscle effect but non-muscle findings — epistaxis, gum bleeding and dilated superficial blood vessels — consistent with interference in BMP9/BMP10–ALK1 vascular signalling. Development of ACE-031 did not resume. Any research use of this molecule should be framed with that outcome in view.
Successor molecules
The class did not end there. More selective ActRII-directed agents, including engineered ligand traps with narrowed binding profiles and monoclonal antibodies against the receptor, were developed subsequently, and several reached approval in haematology and pulmonary indications. ACE-031 is best understood as the first-generation compound whose limitations defined the later designs.
Forms and sizes we supply
| Attribute | Specification |
|---|---|
| Product | ACE-031 |
| Also known as | ActRIIB-Fc, soluble activin receptor type IIB fusion protein, ramatercept |
| Form | Lyophilized recombinant protein, sealed glass vial |
| Available size | 1 mg |
| Purity | ≥95% by SDS-PAGE and HPLC, lot-matched COA available |
| Protein class | Fc-fusion protein; soluble ActRIIB decoy receptor |
| Construct | Extracellular domain of human ActRIIB fused to human IgG1 Fc |
| Quaternary structure | Disulfide-linked homodimer |
| Principal binding partners | Myostatin (GDF-8), activin A, GDF-11, selected BMPs |
| Development history | Acceleron Pharma; clinical development discontinued in 2013 |
| Intended use | Laboratory research only |
The 1 mg vial represents a large molar quantity for a protein used at nanomolar working concentrations, so aliquoting the whole vial on first reconstitution is normal practice. Sourcing considerations are covered in our ACE-031 buying guide.
Reconstitution and storage in a lab context
Fc-fusion proteins are the most fragile category of material on a peptide catalogue and are handled accordingly. Sterile or bacteriostatic water is added slowly down the vial wall and the vial left to stand; vortexing or shaking a large glycoprotein produces shear-induced aggregation that no amount of further mixing reverses. Any persistent haze after dissolution indicates aggregate formation and should be read as a quality problem, not a mixing problem.
The concentration arithmetic is simple — 1 mg made up to 1 mL is 1 mg/mL, and 0.1 mL contains 100 mcg — but experimental working concentrations sit far below this, at which point adsorption to plastic and glass dominates losses. A carrier protein such as 0.1% bovine serum albumin in dilute stocks is standard, and low-binding tubes are preferred. General method is in our reconstitution guide.
Lyophilized vials are held at −20 °C, sealed and protected from light and moisture. Reconstituted material is used at 2–8 °C for immediate work or aliquoted and frozen; repeated freezing and thawing of an Fc-fusion protein reliably generates aggregates and loses activity. Broader guidance is in how to store peptides.
Purity, COA and how to read it
A certificate for a fusion protein carries different information from a peptide certificate, and the informative sections are the non-HPLC ones. SDS-PAGE under reducing and non-reducing conditions should show the monomer and the disulfide-linked dimer at the expected sizes; a non-reducing lane that shows mostly monomer indicates a construct that has not assembled correctly. Size-exclusion chromatography, where provided, quantifies high-molecular-weight aggregate, which is the failure mode that most often explains an inactive vial. Expression system and glycosylation status should be stated, and endotoxin content matters for any cell-based assay. A binding or reporter-assay bioactivity figure is more meaningful than any purity percentage. Our guide to reading a certificate of analysis covers how these sections relate.
Regulatory status
ACE-031 has no marketing authorisation anywhere. Clinical development was discontinued in 2013 and was not resumed, so there is no reference-listed product and no approved labelling for this molecule. Material supplied here is a research-use-only reagent for laboratory investigation by qualified personnel — not a supplement, not a medicine, and not for human or veterinary administration. Myostatin-pathway agents are prohibited in sport under anti-doping rules.
Related molecules and further reading
The two other ways of blocking this axis on our catalogue are Follistatin-344, a broad ligand trap, and GDF-8 / myostatin propeptide, the most ligand-selective of the group. Wider context on how muscle-related research families fit together is in our peptides for muscle growth research overview.