ACE-031 Research, Specifications & Scientific Information

Introduction

ACE-031 is the clearest cautionary tale in this corner of the library, and it earned that position honestly: it worked, and it was stopped anyway.

The compound is a soluble decoy receptor. Myostatin and several related ligands restrain growth in skeletal musculature by signalling through activin type II receptors on the cell surface; ACE-031 is a circulating copy of the receptor's ligand-binding domain, fused to an antibody Fc region so that it persists in plasma, which intercepts those ligands before they reach the real receptor ^[3]. In a phase 1 study in healthy postmenopausal women a single subcutaneous administration produced measurable changes in body composition within four weeks, set out with figures in the human research section below ^[3].

The phase 2 trial in ambulatory boys with Duchenne muscular dystrophy was stopped after the second administration regimen. Not for lack of effect, and not for an effect on musculature: for epistaxis and telangiectasias — nosebleeds and dilated small vessels — which is what broad blockade of this pathway did somewhere the designers were not looking ^[7].

This page is a reference record. It describes research. It contains no guidance of any kind on handling the material.

What Is ACE-031?

ACE-031, whose International Nonproprietary Name is ramatercept, is a recombinant homodimeric fusion protein developed by Acceleron Pharma. It is not a peptide, and it is in this library because it belongs to the same research pathway as the follistatin entries rather than to the same chemical class.

Each of its two identical chains is 343 residues and has two clearly separable parts. The first stretch — roughly the first 110 residues — is the extracellular ligand-binding domain of human activin receptor type IIB. A glycine-glycine-glycine linker then joins it to the C-terminal Fc region of human immunoglobulin G1. The FDA/NCATS Global Substance Registration System records sixteen disulphide links and glycosylation across the assembled dimer, with a calculated average mass of 77,500 g/mol.

The division of labour is the design. The receptor fragment supplies specificity: it binds what the receptor binds. The Fc region supplies persistence, and the measured half-life of 10 to 15 days in humans is what that half of the molecule is for ^[3].

It is not an approved medicine anywhere, and its development was discontinued.

ACE-031 Specifications

ACE-031 carries the International Nonproprietary Name ramatercept and is recorded in the FDA/NCATS Global Substance Registration System under UNII 42HQC6QLEK with CAS registry number 1169766-01-1 and a calculated average mass of 77500 g/mol. It is not a peptide and it is not a small molecule: it is a homodimeric fusion protein. The 343-residue chain above is one of two identical subunits; each consists of the extracellular ligand-binding domain of human activin receptor type IIB joined through a glycine-glycine-glycine linker to the C-terminal Fc region of human immunoglobulin G1, and the register records sixteen disulphide links and glycosylation across the assembled dimer. The single-letter string is therefore one subunit of a molecule that only exists as a pair, and it omits both the disulphide architecture and the carbohydrate. No molecular formula is published by the register and no PubChem compound identifier resolves for the name, so both fields are shown as unknown. The design principle is visible in the sequence itself: the first roughly 110 residues are receptor, the remainder is antibody constant region contributed for the long circulating half-life that an Fc confers.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does ACE-031 Work?

By competing with a receptor for its own ligands.

Myostatin is the best-known of those ligands, and the natural experiment that motivated the whole field is that animals lacking it — engineered mice, and naturally occurring cattle, sheep, dogs and a described human — carry markedly more skeletal musculature. But the decision to build a decoy receptor rather than a myostatin-specific antibody rested on a more specific finding: that more than one ligand signalling through activin type II receptors restrains that growth, so blocking the receptor's whole input produces a larger effect than blocking myostatin alone ^[1].

That breadth is the compound's strength and, as the trial record shows, its problem. A trap at the receptor level cannot distinguish myostatin from activin A or growth and differentiation factor 11, and those ligands are not confined to musculature. Activin signalling participates in vascular biology, and the adverse events that stopped the phase 2 trial were vascular.

The point of intervention also distinguishes this compound from follistatin. Follistatin is a natural binding protein that grips the ligand; ACE-031 is an engineered copy of the surface the ligand is trying to reach. Both end with the ligand neutralised; they differ in where in the recognition event they act, and in what else they touch.

ACE-031 Mechanism of Action

In vitro research

The mechanistic premise was established before the compound existed. Ligands signalling through activin type II receptors were shown to regulate growth in skeletal musculature as a group rather than singly, which is the result that justifies trapping at the receptor rather than at one ligand ^[1].

Comparative characterisation of the activin-targeted constructs developed from that premise — the receptor fusions and their variants — was published by the group that built them ^[5]. A separate line of work approached the same receptor with a blocking antibody rather than a soluble ectodomain, and reported strong hypertrophy and protection from atrophy, which establishes that the pathway rather than the particular construction is doing the work ^[4].

What this in vitro and construct-level literature does not resolve is selectivity. Nothing in the design separates the ligands that act on musculature from those that act elsewhere, because the receptor does not separate them either.

What Is ACE-031 Being Researched For?

Past tense, in every case. Development was discontinued.

• Duchenne muscular dystrophy — the indication that carried the compound into phase 2, in a randomised, double-blind, placebo-controlled ascending-amount trial with an extension study, both terminated ^{[7, 10, 11]}.
• Pathway pharmacology in healthy volunteers — two completed phase 1 studies in healthy postmenopausal women, establishing pharmacokinetics and pharmacodynamics ^{[3, 8, 9]}.
• Preclinical models of neuromuscular disease — soluble activin type IIB receptor administration in mice, including models where the result was unfavourable ^{[2, 6]}.

No registered programme is active, and no approval exists anywhere. Every one of the studies above examined pharmaceutical investigational material under a protocol, and none of them concerns research-grade material supplied for laboratory use.

Human Research on ACE-031

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Phase 1, single ascending amount in healthy postmenopausal women

Population. 48 healthy postmenopausal women, randomised 3:1 to a single subcutaneous administration of the compound from 0.02 to 3 mg/kg or to placebo, in a double-blind design ^{[3, 8]}.

Endpoints. Safety, pharmacokinetics and pharmacodynamics ^[3].

Result. Exposure — both area under the curve and peak concentration — rose linearly with the amount administered, and the mean half-life was 10 to 15 days. At day 29 in the 3 mg/kg group, mean total body lean mass had risen 3.3% by dual-energy X-ray absorptiometry (p = 0.03) and thigh muscle volume 5.1% by magnetic resonance imaging (p = 0.03). Serum biomarker changes were reported as consistent with effects on bone and fat metabolism ^[3].

Adverse events. Generally well tolerated; injection site erythema was among the events reported ^[3].

Limitations. A single administration, 48 participants, one demographic group, and a 29-day readout. It was designed to establish pharmacokinetics and to demonstrate a pharmacodynamic signal, and it did both. It was not designed to detect the events that later stopped development, and it did not.

A second phase 1 study of 70 healthy postmenopausal women is also registered as completed ^[9].

Phase 2 in Duchenne muscular dystrophy, stopped early

Population. Ambulatory boys with Duchenne muscular dystrophy, in a randomised, double-blind, placebo-controlled, ascending-amount trial. Administration was subcutaneous every two to four weeks. The registered enrolment was 24, with 11 in the extension study ^{[7, 10, 11]}.

Primary objective. Safety. Secondary objectives covered pharmacokinetics and pharmacodynamics ^[7].

Result. The study was stopped after the second administration regimen because of potential safety concerns: epistaxis and telangiectasias. The report states that the compound was not associated with serious or severe adverse events. Among the efficacy signals, a trend toward maintenance of six-minute walk distance in the treated groups against a decline in the placebo group was noted and was not statistically significant, together with trends toward increased lean body mass and bone mineral density and reduced fat mass ^[7].

Why it matters, and what it does not show. The events that ended the programme were vascular and had nothing to do with musculature. A compound whose mechanism is the removal of a whole receptor's ligand input will act wherever those ligands act, and this trial is the clinical demonstration of that. The efficacy signals were trends in a study that stopped early, and trends in a truncated trial establish nothing. The authors' own conclusion was that myostatin inhibition remains a promising approach — a statement about the pathway, not a claim about this compound.

Preclinical Research on ACE-031

Animal research

Administration of a soluble activin type IIB receptor to mice promoted growth in skeletal musculature, and did so independent of fibre type — a result that matters because interventions which act only on one fibre population have narrower consequences and narrower risks ^[2].

The result worth dwelling on is a negative one, because it constrains how the pathway should be read. In a mouse model of dysferlinopathy — a muscular dystrophy caused by loss of dysferlin — myostatin inhibition produced hypertrophy as expected, and that hypertrophy accelerated degeneration ^[6]. Making fibres larger in a disease where the membrane repair machinery is defective turned out to be harmful rather than helpful.

That finding sits alongside the Duchenne trial as the second demonstration in this entry that a mechanism which reliably increases mass does not reliably do good. Both belong on the page.

Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

ACE-031 vs Related Compounds

The comparisons below are structural, mechanistic and evidential. No comparison of effect is made on this page.

Follistatin :: A natural secreted binding protein that traps ligands directly. ACE-031 is an engineered copy of the receptor those ligands bind. Both are broad rather than myostatin-selective, and both therefore act on activin and growth and differentiation factor 11 as well ^[1].

Receptor-blocking antibodies

A third approach to the same receptor, using an antibody instead of a soluble ectodomain, which produced strong hypertrophy and protection from atrophy in preclinical work ^[4]. That three different constructions converge on similar effects is evidence about the pathway rather than about any one molecule.

Chemical class

ACE-031 is a 77.5 kDa glycosylated homodimeric fusion protein. The follistatin entries are single-chain secreted glycoproteins. MGF is a 24-residue peptide. These are not comparable materials and are grouped here only by the biology they address.

Evidence base

ACE-031 has the most complete human record of any compound in this group — two completed phase 1 studies and a randomised placebo-controlled phase 2 trial — and that record is why its development stopped. A fuller evidence base is not the same as a more favourable one.

Chemical & Molecular Characteristics

The register record is complete. UNII 42HQC6QLEK in the FDA/NCATS Global Substance Registration System, under the name ramatercept, with CAS registry number 1169766-01-1, a calculated average mass of 77,500 g/mol, and the full sequence of both identical subunits. The register also carries an INN number, a ChEMBL identifier and a DrugBank identifier, which is unusual for a compound in this library and reflects that this one went through formal pharmaceutical development.

The sequence shown is one subunit of two. The molecule exists only as a homodimer. A single-letter string of 343 residues is half of it, and it omits the sixteen disulphide links and the glycosylation that the register records for the assembled protein.

The two halves are visible in the sequence. The N-terminal region is the activin receptor type IIB ectodomain, recognisable by its cysteine-rich pattern; from THTCPPCPAPELLGG onward the chain is the immunoglobulin G1 Fc region, a sequence that appears in many therapeutic fusion proteins for exactly the same reason it appears here.

Two fields are blank on purpose. No molecular formula is published by the register, and no PubChem compound identifier resolves for the name. Both are shown as unknown rather than estimated, and for a glycosylated 77 kDa dimer a single molecular formula would in any case be a simplification rather than a fact.

Frequently Asked Questions

Scientific References

1. Lee SJ, Reed LA, Davies MV, et al.. Regulation of muscle growth by multiple ligands signaling through activin type II receptors Proceedings of the National Academy of Sciences of the United States of America; 2005. PMID 16330774 doi:10.1073/pnas.0505996102
2. Cadena SM, Tomkinson KN, Monnell TE, et al.. Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type Journal of applied physiology (Bethesda, Md. : 1985); 2010. PMID 20466801 doi:10.1152/japplphysiol.00866.2009
3. Attie KM, Borgstein NG, Yang Y, et al.. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers Muscle & nerve; 2013. PMID 23169607 doi:10.1002/mus.23539
4. Lach-Trifilieff E, Minetti GC, Sheppard K, et al.. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy Molecular and cellular biology; 2014. PMID 24298022 doi:10.1128/MCB.01307-13
5. Chen JL, Walton KL, Al-Musawi SL, et al.. Development of novel activin-targeted therapeutics Molecular therapy : the journal of the American Society of Gene Therapy; 2015. PMID 25399825 doi:10.1038/mt.2014.221
6. Lee YS, Lehar A, Sebald S, et al.. Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy Human molecular genetics; 2015. PMID 26206886 doi:10.1093/hmg/ddv288
7. Campbell C, McMillan HJ, Mah JK, et al.. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial Muscle & nerve; 2017. PMID 27462804 doi:10.1002/mus.25268
8. A Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ACE-031 (ActRIIB-IgG1)in Healthy Postmenopausal Volunteers 2008. NCT00755638
9. A Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ACE-031 in Healthy Postmenopausal Women 2009. NCT00952887
10. Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy 2010. NCT01099761
11. Extension Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy 2010. NCT01239758

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.