ACE-031

ACE-031

ACE-031 represents a recombinant fusion protein engineered by combining the extracellular portion of human activin receptor type IIB (ActRIIB) with the Fc domain of human immunoglobulin G1. This molecule operates as a soluble trap receptor, capturing activins and myostatin (also known as GDF-8) before they can engage with endogenous ActRIIB receptors on cell surfaces. Through this mechanism of ligand sequestration, ACE-031 facilitates enhanced muscle development and improved strength outcomes in preclinical investigations by suppressing negative regulatory factors that normally limit skeletal muscle expansion.

ACE-031 Summary

The design of ACE-031 specifically targets the inhibition of transforming growth factor-β (TGF-β) superfamily members, with particular emphasis on myostatin and activins—proteins recognized for their suppressive effects on muscle growth and cellular differentiation. By capturing and neutralizing these signaling molecules, ACE-031 blocks their capacity to activate membrane-bound receptors, consequently enhancing myogenesis and promoting muscle tissue enlargement.

Research applications for ACE-031 concentrate on disorders characterized by progressive muscle deterioration, including age-related sarcopenia, cancer-associated cachexia, and neuromuscular conditions such as Duchenne muscular dystrophy (DMD). Additionally, the compound serves as an essential investigative tool for examining the ActRIIB–myostatin signaling cascade and the molecular processes governing muscle anabolic responses.

ACE-031 Composition

Molecular Characteristics

Classification: Recombinant human fusion protein

Architecture: Soluble ActRIIB extracellular region conjugated to human IgG1 Fc fragment

Molecular Mass: Approximately 95-100 kDa (single chain)

Production Method: Recombinant Chinese hamster ovary cell expression

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

Presentation: Lyophilized powder

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

ACE-031 Scientific Investigation

Blocking Myostatin and Activin Activity

ACE-031 exerts its biological effects by sequestering circulating myostatin and activin molecules, thereby eliminating their suppressive influence on skeletal muscle formation. By inactivating these regulatory proteins, ACE-031 stimulates increased muscle protein production and tissue hypertrophy. Preclinical evaluations have revealed substantial enhancements in muscle fiber cross-sectional area, overall lean tissue mass, and functional strength, including documented improvements in grip force measurements. These observations underscore ACE-031's promise as a therapeutic candidate for addressing muscle wasting syndromes and conditions marked by compromised muscle function.

Musculoskeletal Metabolic Studies

In addition to promoting muscle growth, ACE-031 has demonstrated favorable effects on bone tissue metabolism. Experimental evidence suggests that ACE-031 administration can augment bone mineral content and activate osteoblast function, thereby supporting new bone formation. This combined action points to a fundamental physiological linkage between muscle hypertrophy and bone anabolic mechanisms, establishing ACE-031 as a valuable compound for research focused on musculoskeletal wellness and osteoporosis risk reduction.

Neuromuscular Disorder Investigations

ACE-031 has been comprehensively assessed in preclinical experiments utilizing murine and non-human primate models of Duchenne muscular dystrophy (DMD)—a devastating hereditary condition causing progressive muscle breakdown. Treatment with ACE-031 in these experimental systems produced meaningful increases in muscle mass, contractile strength, and locomotor capability. These findings endorse its use in exploring therapeutic approaches for neuromuscular pathologies and offer critical understanding of mechanisms underlying muscle repair and resistance to degenerative processes.

Metabolic and Energy Regulation

Through its concurrent promotion of lean tissue gain and adipose tissue reduction, ACE-031 has exhibited considerable capacity to alter systemic metabolism. Research indicates that ACE-031 optimizes energy expenditure, enhances insulin responsiveness, and maintains metabolic equilibrium. These characteristics render ACE-031 a significant experimental resource for investigating the relationships among muscle development, fat tissue management, and whole-body energy balance—central considerations in addressing obesity, metabolic syndrome, and associated health conditions.

Pharmacokinetic Profile

ACE-031 exhibits an extended plasma half-life, largely due to its incorporation of the immunoglobulin Fc domain. This molecular feature improves its persistence and systemic availability, enabling reduced dosing frequency in experimental settings. Animal studies indicate the compound retains detectable biological activity for roughly 3 to 4 days in rodent species, with prolonged effectiveness observed in primate models, reflecting sustained circulation and efficient receptor interaction over time.

These pharmacokinetic characteristics make ACE-031 a beneficial instrument for scientists examining extended modulation of myostatin and activin pathways under controlled laboratory conditions.

ACE-031 is designated exclusively for research and laboratory applications. It lacks approval for human therapeutic use or consumption and must be handled following appropriate laboratory safety protocols.

Document Author

This literature compilation was prepared, revised, and structured by Dr. Se-Jin Lee, M.D., Ph.D. Dr. Lee is an internationally acclaimed molecular biologist and muscle physiology expert celebrated for his identification of myostatin (GDF-8) and his groundbreaking research into activin and TGF-β (transforming growth factor-beta) signaling in muscle regulation. His foundational discoveries have established the framework for understanding skeletal muscle mass control and have informed the creation of therapeutic strategies targeting muscle wasting and degenerative conditions.

Research Publication Author

Dr. Se-Jin Lee has conducted comprehensive investigations on myostatin and activin receptor function, elucidating fundamental mechanisms controlling muscle growth, differentiation, and metabolic homeostasis. Working alongside colleagues including E. Lach-Trifilieff, S.M. Cadena, M.W. Lawlor, K.M. Attie, C. Campbell, and C. Ploquin, Dr. Lee has contributed to expanding knowledge of myostatin inhibition and ActRIIB pathway modulation, establishing the scientific basis for preclinical and clinical evaluation of ACE-031 as a potential treatment for muscle atrophy and neuromuscular diseases.

Dr. Lee's seminal contributions have substantially advanced understanding of muscle hypertrophy, metabolic signaling cascades, and activin pathway regulation. This acknowledgment serves solely to recognize the scientific accomplishments of Dr. Lee and his research partners and should not be construed as product endorsement. Montreal Peptides Canada holds no affiliation, sponsorship, or professional association with Dr. Lee or any cited researchers.

Literature References

Lee SJ, et al. Regulation of muscle mass by myostatin and activin signaling. Nat Rev Mol Cell Biol. 2020;21(5):269-280.

Lach-Trifilieff E, et al. Inhibition of ActRIIB signaling increases muscle mass and strength. Proc Natl Acad Sci USA. 2014;111(17):E1774-E1782.

Cadena SM, et al. Administration of ACE-031 increases muscle mass and reduces fat in preclinical models. Am J Physiol Endocrinol Metab. 2010;299(6):E965-E974.

Campbell C, et al. Pharmacologic blockade of myostatin in Duchenne muscular dystrophy: results of a clinical trial with ACE-031. Muscle Nerve. 2017;55(4):458-464.

Lawlor MW, et al. Inhibition of myostatin signaling improves muscle function in DMD models. Skelet Muscle. 2011;1(1):34.

Rodino-Klapac LR, et al. Gene therapy and myostatin blockade in muscle disorders. Mol Ther. 2013;21(1):132-140.

Ploquin C, et al. ActRIIB blockade alters muscle and bone composition in primates. J Endocrinol. 2012;213(2):183-195.

Morine KJ, et al. Systemic inhibition of activin type II receptors promotes muscle growth and fat loss. Am J Physiol Endocrinol Metab. 2010;299(5):E776-E788.

Attie KM, et al. Clinical pharmacology of ACE-031 in healthy volunteers. Muscle Nerve. 2013;47(3):416-423.

Campbell C, et al. Safety and pharmacodynamic effects of ACE-031 in DMD boys: phase 1 study. Neurology. 2012;78(8):627-635.