ACE-031 1mg
ACE-031 (Soluble Activin Receptor Type IIB-Fc Fusion)
ActRIIB extracellular domain fused to human IgG1 Fc region
Overview
ACE-031 is a soluble decoy receptor constructed by fusing the extracellular domain of activin receptor type IIB (ActRIIB) with the Fc region of human IgG1. This creates a circulating 'trap' that binds and neutralizes myostatin, activin A, GDF-11, and other TGF-beta superfamily ligands before they can interact with cell-surface ActRIIB receptors on muscle cells. By sequestering myostatin (the primary negative regulator of muscle growth), ACE-031 removes the brake on muscle protein synthesis and satellite cell activation. The result is increased muscle mass through both hypertrophy (larger fibers) and hyperplasia (more fibers). Because ACE-031 also binds activins and GDF-11, its effects extend beyond pure myostatin blockade — it broadly antagonizes the TGF-beta/SMAD2/3 signaling axis that suppresses muscle growth. ACE-031 was developed by Acceleron Pharma and advanced to Phase II clinical trials for Duchenne muscular dystrophy (DMD). While it demonstrated significant lean mass gains (approximately 3% increase in total body lean mass after a single dose in healthy volunteers), development was suspended due to minor but unacceptable off-target effects including epistaxis and telangiectasia, likely related to its broad ligand-trapping activity affecting BMP9/10 (vascular remodeling ligands). The successor compound ACE-2494 was designed with refined selectivity.
Mechanism of Action
ACE-031 is a soluble decoy receptor constructed by fusing the extracellular domain of activin receptor type IIB (ActRIIB) with the Fc region of human IgG1. This creates a circulating 'trap' that binds and neutralizes myostatin, activin A, GDF-11, and other TGF-beta superfamily ligands before they can interact with cell-surface ActRIIB receptors on muscle cells. By sequestering myostatin (the primary negative regulator of muscle growth), ACE-031 removes the brake on muscle protein synthesis and satellite cell activation. The result is increased muscle mass through both hypertrophy (larger fibers) and hyperplasia (more fibers). Because ACE-031 also binds activins and GDF-11, its effects extend beyond pure myostatin blockade — it broadly antagonizes the TGF-beta/SMAD2/3 signaling axis that suppresses muscle growth. ACE-031 was developed by Acceleron Pharma and advanced to Phase II clinical trials for Duchenne muscular dystrophy (DMD). While it demonstrated significant lean mass gains (approximately 3% increase in total body lean mass after a single dose in healthy volunteers), development was suspended due to minor but unacceptable off-target effects including epistaxis and telangiectasia, likely related to its broad ligand-trapping activity affecting BMP9/10 (vascular remodeling ligands). The successor compound ACE-2494 was designed with refined selectivity.
Key Research Findings
- Attie et al. (2013) demonstrated ACE-031 increased lean body mass by 3.3% and thigh muscle volume by 5.1% after a single dose in healthy postmenopausal women.
- Lee et al. (2005) showed soluble ActRIIB-Fc increases muscle mass by 40-60% in wild-type mice over 4 weeks, with effects in both muscles directly targeted by myostatin and those less dependent on it.
- Campbell et al. (2017) reported Phase II results in DMD patients showing improvements in lean mass and bone mineral density.
- Cadena et al. (2010) demonstrated ActRIIB-Fc increases muscle mass in both young and aged mice, suggesting potential for age-related sarcopenia.
Citations & References
A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers
Attie KM, Borgstein NG, Yang Y, et al. — Muscle Nerve (2013)
Regulation of muscle growth by multiple ligands signaling through activin type II receptors
Lee SJ, Reed LA, Davies MV, et al. — Proc Natl Acad Sci USA (2005)
Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type
Cadena SM, Tomkinson KN, Monnell TE, et al. — J Appl Physiol (2010)
Dosage in Research
Clinical trials used single IV doses of 0.02-3 mg/kg. Mouse studies used 10 mg/kg IP twice weekly. The 1mg vial provides material for in vitro binding assays and small animal studies.
Dosage information is derived from published research literature and is presented for educational purposes only. This is not medical advice. All products are for laboratory research use only.
Storage & Handling
Store lyophilized (freeze-dried) powder at -20°C to 4°C in a dry environment protected from light. Unreconstituted peptide is stable for extended periods when stored properly.
Once reconstituted with bacteriostatic water or an appropriate solvent, store at 2-8°C and use within the timeframe specified on the Certificate of Analysis. Avoid repeated freeze-thaw cycles.
A Certificate of Analysis documenting purity, identity, and recommended storage conditions is included with every order.
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Research Use Only
All products are intended for laboratory research and educational purposes only. Products have not been evaluated by the FDA and are not intended for human consumption, diagnosis, treatment, or prevention of any disease. Purchasers must be 21+ and confirm research use intent.