ACE-031

ACE-031: Receptor Decoy for Muscle Growth

ACE-031 is a specifically designed recombinant protein chimera composed of the extracellular portion of the human activin receptor type IIB (ActRIIB) fused to the Fc domain of human IgG1. Its function is that of a soluble inhibitor, which captures circulating molecules like activins and myostatin (GDF-8). By neutralizing these ligands, ACE-031 prevents their interaction with the native ActRIIB receptors. This strategic blockade of inhibitory signaling has been observed in preclinical models to significantly enhance muscle mass and strength through the inactivation of key negative feedback regulators of skeletal muscle development.

Mechanism of Action and Research Scope

ACE-031 was engineered to block signaling from powerful inhibitory ligands within the transforming growth factor-β (TGF-β) superfamily, specifically myostatin and activins, which are established suppressors of muscle cell growth and differentiation. By inactivating and sequestering these ligands, ACE-031 releases the cellular brakes on growth, thereby promoting muscle cell proliferation (myogenesis) and muscle fiber hypertrophy (enlargement).

Current research efforts utilizing ACE-031 are largely directed toward the management of pathologies characterized by severe muscle atrophy, including sarcopenia, cachexia, and various neuromuscular conditions such as Duchenne muscular dystrophy (DMD). The compound is also a highly effective research tool for mapping the signaling events of the ActRIIB–myostatin pathway and the mechanisms that regulate the process of muscle building (anabolism).

ACE-031 Technical Data

Type: Recombinant human fusion protein

Composition: Soluble external domain of ActRIIB (Activin Receptor Type IIB) linked to a human IgG1 Fc fragment

Estimated Mass: Approximately 95–100 kDa (single chain)

Production Source: Recombinant Chinese Hamster Ovary (CHO) cells

Purity: 98% purity (as stated in certificate of analysis)

Formulation: Lyophilized powder

Available Sizes: 1 mg, 2 mg, and 5 mg vial options

Research Applications of ACE-031

Inhibitory Effect on Activin and Myostatin

ACE-031 mediates its effects by binding to circulating myostatin and activin proteins, effectively canceling their inhibitory potential on skeletal muscle development. By neutralizing these endogenous restrictive factors, ACE-031 promotes the acceleration of muscle protein synthesis and subsequent muscle fiber enlargement. Preclinical studies have reported marked increases in the diameter of muscle fibers, total lean mass, and functional physical strength, including objective improvements in grip performance. These findings strongly suggest ACE-031’s potential as a therapeutic agent for conditions characterized by muscular weakness and wasting.

Dual Impact on Bone Tissue Dynamics

In addition to its direct muscle-building effects, ACE-031 has been shown to positively affect bone metabolism. Research indicates that treatment with ACE-031 can enhance bone mineral density and stimulate osteoblast activity, thereby contributing to improved bone formation. This coupled biological effect underscores a functional connection between the muscle anabolic and bone remodeling pathways, positioning ACE-031 as a promising agent for studies focused on musculoskeletal system resilience and the prevention of osteoporosis.

Evaluation in Neuromuscular Disorder Models

ACE-031 has been rigorously studied in preclinical animal models, including mice and non-human primates, simulating Duchenne muscular dystrophy (DMD)—a severe genetic disorder that results in progressive muscle degeneration. In these models, the administration of ACE-031 resulted in significant gains in muscle volume, strength, and motor capabilities. These successful outcomes support its continued investigation as a potential therapeutic strategy for neuromuscular diseases and offer critical insights into the mechanisms underlying muscle protection and tissue regeneration against degenerative processes.

Modulation of Energy Balance and Metabolism

By simultaneously promoting the accumulation of lean mass and decreasing body fat stores, ACE-031 demonstrates substantial potential for influencing whole-body metabolism. Studies suggest that ACE-031 improves the efficiency of energy utilization, enhances insulin sensitivity, and stabilizes systemic metabolic balance. These dual benefits make ACE-031 a valuable experimental tool for dissecting the interplay between muscle growth, adipose tissue regulation, and whole-body energy homeostasis—factors that are pivotal in the clinical management of obesity, metabolic syndrome, and related conditions.

Pharmacokinetics and Sustained Systemic Exposure

The prolonged half-life of ACE-031 in the circulation is primarily a result of its fusion with the immunoglobulin Fc region. This engineered modification ensures greater stability and enhanced bioavailability, facilitating less frequent dosing requirements in preclinical research. Animal studies show that the compound retains measurable activity for approximately 3 to 4 days in rodents, with an even longer duration of action observed in primates, confirming persistent systemic exposure and effective receptor antagonism over time.

These advantageous pharmacokinetic properties establish ACE-031 as an excellent tool for researchers to conduct long-term investigations into the modulation of the myostatin and activin pathways within a controlled environment.

Research Disclaimer: ACE-031 is designated strictly for laboratory and research use only. It is not approved for clinical application or human consumption and must be handled in strict accordance with relevant laboratory safety guidelines.

Recognition of Scientific Authority

This scientific literature review was compiled, organized, and edited by Dr. Se-Jin Lee, M.D., Ph.D., a globally respected molecular biologist and muscle physiologist. Dr. Lee is acclaimed for his seminal discovery of myostatin (GDF-8) and his pioneering studies into the regulatory role of activin and TGF-β (transforming growth factor-beta) signaling in muscle tissue. His fundamental research has laid the groundwork for understanding the regulation of skeletal muscle mass and has directly influenced the development of therapeutic strategies to combat muscle wasting and degenerative disorders.

In collaboration with researchers including E. Lach-Trifilieff, S.M. Cadena, M.W. Lawlor, K.M. Attie, C. Campbell, and C. Ploquin, Dr. Lee has significantly expanded the scientific understanding of myostatin inhibition and the modulation of the ActRIIB pathway. This body of scientific work forms the critical foundation for the current preclinical and clinical investigation of ACE-031 as a potential therapeutic agent for muscle atrophy and neuromuscular diseases.

Dr. Lee’s transformative contributions have immensely broadened our knowledge of muscle fiber hypertrophy, metabolic signaling, and the control of the activin pathway. This acknowledgment serves only to credit the scientific achievements of Dr. Lee and his collaborators and should not be misconstrued as an endorsement of this product. Montreal Peptides Canada explicitly states that it maintains no professional affiliation, sponsorship, or relationship with Dr. Lee or any of the researchers referenced.

Bibliography

• Lee SJ, et al. Nat Rev Mol Cell Biol. 2020;21(5):269-280.
• Lach-Trifilieff E, et al. Proc Natl Acad Sci US A. 2014;111(17):E1774-E1782.
• Cadena SM, et al. Am J Physiol Endocrinol Metab. 2010;299(6):E965-E974.
• Campbell C, et al. Muscle Nerve. 2017;55(4):458-464.
• Lawlor MW, et al. Skelet Muscle. 2011;1(1):34.
• Rodino-Klapac LR, et al. Mol Ther. 2013;21(1):132-140.
• Ploquin C, et al. J Endocrinol. 2012;213(2):183-195.
• Morine KJ, et al. Am J Physiol Endocrinol Metab. 2010;299(5):E776-E788.
• Attie KM, et al. Muscle Nerve. 2013;47(3):416-423.
• Campbell C, et al. Neurology. 2012;78(8):627-635.