ACE 031 [Peptide]

Description

What is ACE-031?

ACE-031 is a recombinant fusion protein composed of the extracellular ligand-binding domain of activin receptor type IIB (ActRIIB) joined to the Fc region of human immunoglobulin G1 (IgG1). This molecular architecture produces a soluble decoy receptor — referred to in the research literature as a ligand trap — that competes with membrane-bound ActRIIB on target cell surfaces for binding of endogenous ligands, most notably myostatin (GDF-8), GDF-11, and activin A. By sequestering these ligands extracellularly before they can engage native cell-surface ActRIIB, ACE-031 prevents downstream SMAD2/3 phosphorylation — the primary intracellular cascade through which myostatin and activin A suppress skeletal muscle protein synthesis and promote atrophy-related gene expression.

ACE-031 was originally developed by Acceleron Pharma and has been investigated across a range of preclinical animal models and early-phase clinical research settings. It exists in two research forms: the full recombinant ActRIIB-Fc fusion protein biologic (≈101 kDa) and a synthetic peptide fragment analog (≈5.8 kDa) used in laboratory binding and cell-based assays. The RCDbio formulation is supplied as a research-grade lyophilized powder in a sterile, sealed glass vial — not a nasal spray, sublingual tablet, or any other pre-formulated delivery format.

ACE-031 is not approved by the Food and Drug Administration for human or veterinary use in this research-grade, non-pharmaceutical form. It is not a dietary supplement and is intended strictly for laboratory and research purposes.

Chemical Properties

Property	Detail
Product Type	Recombinant Fusion Protein (ActRIIB-Fc Ligand Trap)
Product Name	ACE-031
Application	Scientific / Research Use Only
CAS Number	N/A — recombinant biologic; no CAS registry entry for the intact fusion protein
Molar Mass	≈101 kDa (intact ActRIIB-Fc fusion form); ≈5.8 kDa (synthetic peptide fragment analog form)
Chemical Formula	Not applicable for intact biologic; ≈C₂₆₆H₄₇₂N₈₀O₉₆S₆ (peptide fragment analog form, approximate)
Sequence	ActRIIB extracellular domain (residues 25–131 of human ACVR2B) fused to human IgG1 hinge-CH2-CH3 Fc region
IUPAC Name	Not applicable — recombinant protein; no assigned IUPAC systematic name
Synonyms	ActRIIB-Fc, ACVR2B-Fc, soluble activin type IIB receptor, ruxolitinib-unrelated ActRIIB decoy
Physical Form	Lyophilized white to off-white powder
Solubility	Soluble in sterile water or phosphate-buffered saline (PBS); reconstitute gently to avoid foaming and protein aggregation
Storage (Lyophilized)	−20°C long-term; 2–8°C for short-term use; sealed vial; protect from light and moisture; include desiccant
Storage (Reconstituted)	2–8°C; use within 24–48 hours of reconstitution; avoid repeated freeze-thaw cycles, which degrade Fc-domain integrity
PubChem CID	Not applicable — recombinant biologic protein; no assigned PubChem CID
Purity	≥98% (HPLC verified, independent third-party laboratory analysis; COA available per batch)
WADA Status	ACE-031 is explicitly named on the 2026 WADA Prohibited List under S4.3 (Agents Preventing Activin Receptor IIB Activation) as a “decoy activin receptor.” This is a non-Specified Substance, prohibited at all times in- and out-of-competition. Researchers engaged in sport-adjacent studies should verify the current status at GlobalDRO.com before use.

How Does ACE-031 Work?

ACE-031 functions as a soluble decoy receptor by presenting the ActRIIB extracellular ligand-binding domain in circulating form, competing with membrane-anchored ActRIIB for a shared pool of endogenous TGF-β superfamily ligands.

Ligand Trapping and ActRIIB Competitive Inhibition

In cell-free and cell-based systems, ACE-031 binds myostatin (GDF-8), GDF-11, and activin A with high affinity, sequestering them in the extracellular space before they can engage native cell-surface ActRIIB. This competitive displacement prevents receptor dimerization and subsequent recruitment of downstream signaling intermediaries. In preclinical murine skeletal muscle preparations, this mechanism has been characterized as preventing SMAD2 and SMAD3 phosphorylation — the primary transcription factor activation step through which myostatin and activin A drive atrophy gene expression, including upregulation of MuRF-1 and atrogin-1.

Myostatin and GDF-11 Inhibition in Skeletal Muscle Models

In preclinical C57BL/6 mouse models and common marmoset (Callithrix jacchus) in vivo systems, ACE-031 administration has been associated with significant increases in lean body mass, individual muscle group weights, and muscle fiber cross-sectional area in both type I and type II fiber populations. In 14-week marmoset dosing studies, ACE-031-treated subjects demonstrated increased biceps brachii cross-sectional area and improved ex vivo contractile force production in extensor digitorum longus (EDL) preparations compared to vehicle controls.

Activin A Co-Inhibition and Dual-Ligand Coverage

Because circulating activin A levels in primates and humans are reported to be substantially higher than in rodents, dual inhibition of both myostatin and activin A is considered mechanistically important in primate-relevant muscle biology research. ACE-031’s binding profile spans both ligands simultaneously, distinguishing it from myostatin-selective antibody tools. In phase I clinical research in healthy post-menopausal women, a single dose of ACE-031 at 3 mg/kg was associated with a 3.3% increase in total lean mass and a 5.1% increase in thigh muscle volume at day 29 as assessed by DEXA and MRI, respectively.

Bone Metabolism and Osteoclast Pathway Research

In a preclinical female C57Bl/6 N mouse ovariectomy (OVX) model of postmenopausal bone loss, ActRIIB-Fc treatment at 5 mg/kg administered intraperitoneally once weekly for seven weeks prevented bone mass decline relative to PBS-treated OVX controls, as assessed by microCT imaging and histomorphometric analysis. The mechanism was characterized as reduced osteoclast number and function, suggesting that ActRIIB ligand sequestration modulates the RANKL/OPG bone remodeling axis independently of its skeletal muscle effects. Glucose clearance was impaired in ActRIIB-Fc-treated groups in both sham and OVX conditions in this model, highlighting a metabolic variable researchers should account for in experimental designs.

Adipose Tissue and Body Composition Research

In the same OVX preclinical model, ActRIIB-Fc treatment attenuated OVX-induced adipocyte hypertrophy and reduced systemic adipose tissue accumulation compared to PBS-treated OVX controls, as quantified by tissue histology. These findings have supported the use of ACE-031 and related ActRIIB constructs as research tools in body composition studies examining the interaction between TGF-β ligand activity, lean mass regulation, and adipose depot dynamics.

Key Research Findings

• Lean mass increase in healthy volunteers: In a double-blind, placebo-controlled phase I study in post-menopausal women, a single 3 mg/kg subcutaneous dose produced a statistically significant 3.3% increase in total lean mass (DEXA) and 5.1% increase in thigh muscle volume (MRI) at day 29. [Attie et al., 2013]
• DMD preclinical and clinical pharmacodynamics: In a randomized, placebo-controlled trial in ambulatory DMD boys, ACE-031 produced dose-dependent increases in lean mass and trends toward maintained 6-minute walk distance; the study was terminated after the second dosing cohort due to epistaxis and telangiectasias. [Campbell et al., 2017]
• Bone protection in OVX murine models: ActRIIB-Fc at 5 mg/kg weekly for seven weeks prevented bone mass loss in OVX female C57Bl/6 N mice as assessed by microCT; osteoclast count and function were significantly reduced. [Puolakkainen et al., 2022]
• NHP muscle mass and contractile function: In 14-week common marmoset in vivo dosing studies, ACE-031 produced significant increases in lean mass, biceps brachii fiber cross-sectional area, and EDL absolute and specific force production vs. vehicle controls. [Winbanks et al., 2025]
• Adverse event mechanism identified: Off-target BMP9 inhibition — a ligand critical for endothelial cell vascular remodeling — is the proposed mechanism for epistaxis and telangiectasia observed in clinical research settings; BMP9 binds ActRIIB with sufficient affinity to be co-inhibited by ACE-031.

All findings listed above are derived from preclinical or in vitro data, or from early-phase clinical safety and pharmacodynamics research. No conclusions regarding human therapeutic efficacy can be drawn from these observations. These findings do not constitute evidence of safety or efficacy in any human condition or organism.

What are the Potential Research Applications of ACE-031?

ActRIIB Ligand Binding Kinetics and Selectivity Studies

ACE-031 is used in controlled in vitro binding assay systems to characterize the affinity, specificity, and competitive binding kinetics of ActRIIB for its endogenous ligands — including myostatin, GDF-11, activin A, activin B, and BMP9. Structure-activity relationship (SAR) studies employ ACE-031 as a reference construct against modified ActRIIB domain variants to map residues critical for ligand selectivity.

SMAD2/3 Pathway Suppression Research in Skeletal Muscle Cell Systems

In primary myotube cultures and immortalized skeletal muscle cell lines, ACE-031 is employed to suppress SMAD2/3 phosphorylation downstream of ActRIIB, enabling researchers to interrogate the transcriptional consequences of TGF-β superfamily ligand blockade on atrophy gene expression, satellite cell activation, and protein synthesis rate.

Skeletal Muscle Hypertrophy and Wasting Model Research

In rodent and non-human primate in vivo systems, ACE-031 serves as a pharmacological tool for studying the physiological consequences of ActRIIB ligand blockade on muscle fiber size, fiber number, contractile properties, and body composition. These systems are employed in preclinical muscle wasting and dystrophy pathway research.

Bone Remodeling and Osteoporosis Model Research

In preclinical OVX, fracture repair, and aging models, ActRIIB-Fc constructs have been investigated for their capacity to modulate osteoclast-mediated bone resorption and support trabecular bone volume maintenance. ACE-031 serves as a reference agent in studies examining the intersection of TGF-β superfamily signaling with bone remodeling pathway regulation.

Dual Myostatin/Activin A Inhibition Comparative Studies

ACE-031 enables direct comparison of broad-spectrum ActRIIB ligand blockade against myostatin-selective antibody tools in the same experimental system, supporting mechanistic inquiry into which TGF-β superfamily ligands are rate-limiting for muscle mass regulation in primate-relevant model systems.

These are observed in preclinical and in vitro contexts only and do not constitute claims of efficacy or safety in any organism.

What are the Potential Side Effects of ACE-031?

• Epistaxis (nosebleeds) and telangiectasias (small dilated blood vessels) observed in both DMD pediatric patients and healthy adult volunteers in clinical research settings; attributed in later analyses to off-target BMP9 inhibition, a ligand involved in vascular endothelial remodeling
• Injection site erythema observed at higher dose groups (3 mg/kg) in the phase I healthy volunteer study; it was characterized as non-serious and transient
• Impaired glucose clearance observed in both SHAM and OVX murine preclinical groups treated with ActRIIB-Fc at 5 mg/kg; effect was not dose-response characterized across full range in the published study
• Dose-dependent increases in serum follistatin and decreases in follicle-stimulating hormone (FSH) noted as pharmacodynamic biomarker shifts in healthy volunteer clinical research; long-term implications not established
• Long-term or chronic toxicity data for this research-grade preparation have not been established
• No human safety data has been established for this research-grade formulation. These observations are derived from experimental systems and should not be extrapolated to human or animal outcomes.

Risk & Handling

Risk Tier: HIGH

ACE-031 is a pharmacologically active recombinant fusion protein with broad TGF-β superfamily ligand-trapping activity. Its off-target inhibition of BMP9 and BMP10 demonstrated to affect vascular remodeling signaling in clinical research contexts — elevates the risk tier above that of single-target peptides. Dose-dependent pharmacodynamic effects on muscle mass, bone remodeling, hematopoiesis, and glucose metabolism have been characterized in preclinical systems. No human safety data has been established for this research-grade preparation.

Handling Precautions

ACE-031 lyophilized vials must be handled exclusively in a controlled laboratory environment by trained personnel with appropriate experience in recombinant protein handling. Required PPE: nitrile gloves, a laboratory coat, and eye protection at minimum. Reconstitution should be performed using aseptic technique; avoid vigorous agitation or vortexing, which can induce protein aggregation and denaturation. Do not generate aerosols during reconstitution. Avoid direct skin and eye contact with lyophilized powder and reconstituted solution.

Exposure Risks

No human safety data has been established for this research-grade formulation. BMP9 cross-inhibition has been characterized as a mechanism for vascular adverse events in clinical research settings and represents a compound-specific hazard distinct from its myostatin inhibition activity. Chronic toxicity, immunogenicity, and organ-specific toxicity data for this research-grade preparation do not exist. The plasma half-life of ACE-031 in clinical pharmacokinetic studies was approximately 10–15 days following a single subcutaneous dose, indicating prolonged systemic exposure following reconstituted solution handling.

Storage

• Lyophilized form: Store at -20°C in sealed, light-protected vial with desiccant
• Reconstituted form: Store at 2–8°C; use within 24–48 hours of reconstitution
• Avoid repeated freeze-thaw cycles; IgG1 Fc-domain fusion proteins undergo progressive aggregation with each freeze-thaw cycle, reducing binding activity
• Do not store reconstituted solution in the presence of metal ion contaminants or non-physiological pH conditions
• Discard any reconstituted solution that appears turbid, discolored, or shows visible particulate matter

FAQs

Q: What is ACE-031 and what is it investigated for in research? A: ACE-031 is a recombinant fusion protein composed of the extracellular domain of activin receptor type IIB (ActRIIB) linked to a human IgG1 Fc region. In laboratory settings, it is investigated as a soluble decoy receptor or ligand trap for myostatin (GDF-8), GDF-11, and activin A, which are negative regulators of skeletal muscle mass. It has been employed as a pharmacological tool in preclinical skeletal muscle, bone remodeling, and body composition research models.

Q: What is the plasma half-life of ACE-031 in preclinical and clinical research models? A: In the phase I single ascending-dose clinical study in healthy post-menopausal women, ACE-031 exhibited a mean plasma half-life (T½) of 10–15 days following a single subcutaneous dose, with AUC and Cmax increasing linearly with dose. These figures are derived from a specific clinical pharmacokinetic research context and do not represent safety or tolerability data for the research-grade formulation supplied here.

Q: How should ACE-031 be stored to maintain stability? A: Lyophilized ACE-031 vials should be stored at −20°C in a sealed, light-protected container with desiccant. For short-term use, storage at 2–8°C is permissible. Once reconstituted, the solution should be stored at 2–8°C and used within 24–48 hours. Repeated freeze-thaw cycles must be avoided, as IgG1 Fc-domain fusion proteins undergo progressive aggregation with each cycle, reducing their ligand-binding activity. Discard any reconstituted solution showing turbidity, discoloration, or particulate matter.

Q: What toxicity observations have been reported in preclinical and clinical research studies? A: In clinical research settings, epistaxis (nosebleeds), telangiectasias, and gum bleeding were reported in both DMD pediatric subjects and healthy adult volunteers; later mechanistic analyses attributed these findings to off-target BMP9 inhibition by ACE-031. Injection site erythema was observed at the 3 mg/kg dose group in healthy volunteers. In a preclinical ovariectomy mouse model, impaired glucose clearance was observed in ActRIIB-Fc-treated animals. These observations reflect findings from specific experimental systems and should not be extrapolated to any other context.

Q: What is ACE-031 typically reconstituted with in laboratory research? A: ACE-031 is typically reconstituted in sterile water or phosphate-buffered saline (PBS) in published preclinical protocols. Reconstitution should be performed by gently swirling — not vortexing to avoid protein aggregation. Researchers should consult batch-specific Certificate of Analysis documentation and the relevant primary literature for concentration and vehicle specifications appropriate to their experimental system.

Q: How does ACE-031 differ from anti-myostatin antibody tools in preclinical research? A: Anti-myostatin antibodies selectively target the myostatin ligand. ACE-031, as a soluble ActRIIB decoy receptor, simultaneously captures a broader spectrum of ActRIIB ligands  including myostatin, GDF-11, activin A, and BMP9. This broader coverage reflects the native ligand promiscuity of the ActRIIB receptor. In preclinical systems where activin A circulates at higher concentrations relative to myostatin  as is the case in primates  the dual coverage provided by ACE-031 may produce different experimental outcomes than myostatin-selective tools, a factor researchers must account for in model design and result interpretation.

Q: How does research-grade ACE-031 differ from the pharmaceutical-development form of the compound? A: The pharmaceutical-development form of ACE-031 was a GMP-manufactured recombinant biologic produced under controlled conditions with validated immunogenicity and pharmacokinetic profiling for clinical trial administration. The research-grade lyophilized preparation supplied by RCDbio is not GMP-manufactured, is not validated for clinical or veterinary administration, and has no established human safety profile. It is supplied exclusively as a laboratory tool for in vitro and preclinical research use by qualified investigators.

Related Research Compounds

BPC-157 Peptide A stable gastric pentadecapeptide investigated in preclinical models for its interactions with growth hormone receptor signaling and tissue regeneration pathways; relevant to comparative anabolic signaling research.

GDF-8 (Myostatin) Peptide The primary endogenous ligand inhibited by ACE-031; investigated in preclinical systems as the reference negative regulator of skeletal muscle hypertrophy and hyperplasia via ActRIIB-SMAD2/3 pathway activation.

GHRP-6 Peptide A synthetic hexapeptide ghrelin receptor agonist investigated in preclinical models for GH secretagogue activity and metabolic pathway interactions; relevant to comparative body composition and anabolic signaling research.

All products listed are for laboratory and research purposes only.

References

1. Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML. (2013). A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle & Nerve, 47(3):416–423. https://pubmed.ncbi.nlm.nih.gov/23169607/
   
2. Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, Selby K, McClure T, Wilson DM, Sherman ML, Escolar D, Attie KM. (2017). Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle & Nerve, 55(4):458–464. https://pubmed.ncbi.nlm.nih.gov/27462804/
   
3. Puolakkainen T, Rummukainen P, Pihala-Nieminen V, Ritvos O, Savontaus E, Kiviranta R. (2022). Treatment with soluble activin type IIB receptor ameliorates ovariectomy-induced bone loss and fat gain in mice. Calcified Tissue International, 110(4):504–517. https://pubmed.ncbi.nlm.nih.gov/35024891/
   
4. Dschietzig TB, Bartsch C, Richter C, Laule M, Baumann G, Stangl K. (2019). Systemic blockade of ACVR2B ligands protects myocardium from acute ischemia-reperfusion injury. International Journal of Cardiology, 280:27–33. https://pubmed.ncbi.nlm.nih.gov/30765322/
   

Disclaimer

ACE-031 is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

The Food and Drug Administration has not evaluated the statements on our website. This product is not approved for human or veterinary use. Researchers must comply with all applicable local, state, and federal laws and regulations governing the purchase and use of research compounds. By purchasing, you agree to our Terms and Conditions. RCDbio reserves the right to refuse sales to unauthorized individuals.

ATTENTION: All RCDbio products are strictly for LABORATORY AND RESEARCH PURPOSES ONLY. They are not intended for human consumption, veterinary use, or any other non-research application. For queries, complaints, or support, contact support@rcdbio.co