ACE-031

ACE-031 is a synthetic fusion protein designed to act as a decoy for the activin receptor type IIB (ActRIIB), a key receptor for myostatin and related TGF-β superfamily members that suppress muscle growth. By binding to and neutralizing these ligands, ACE-031 prevents them from activating their natural receptors, enabling significant skeletal muscle hypertrophy and improved strength. It also positively affects bone metabolism and adipose tissue regulation, making it a promising research agent in muscle-wasting diseases and metabolic disorders. ACE-031 is a recombinant protein that combines the extracellular domain of the ActRIIB receptor with the Fc portion of human IgG1, allowing it to circulate and bind ligands like myostatin (GDF-8), activin A, BMP-2, and BMP-7. These molecules typically limit muscle development through Smad2/3 signaling cascades. By sequestering these ligands, ACE-031 enables uninhibited muscle cell proliferation and hypertrophy, increasing lean body mass, strength, and potentially enhancing mitochondrial efficiency and bone density. Its long half-life (10–15 days) supports infrequent dosing in experimental models.

- Promote muscle hypertrophy and protect against muscle wasting

- Improve muscle strength, bone density, and metabolic function

How this peptide works in the body

Myostatin & Activin A Inhibition:

ACE-031 binds circulating myostatin and activin A, preventing them from activating ActRIIB. Myostatin normally inhibits satellite cell proliferation and muscle protein synthesis through Smad2/3 signaling. By blocking this axis, ACE-031 enables enhanced muscle regeneration, hypertrophy, and reduced protein degradation.

TGF-β Superfamily Blockade:

Besides myostatin, ACE-031 also inhibits other ligands like BMP-2 and BMP-7, which influence both muscle and bone tissue regulation. This broader inhibition enhances skeletal muscle growth and may stimulate osteoblast differentiation while reducing osteoclast activity.

Energy Metabolism Enhancement:

Inhibition of ActRIIB increases PPARβ and PGC-1α expression, upregulating oxidative metabolism in muscle cells. This improves mitochondrial density, fatty acid oxidation, and lactate clearance, reducing fatigue and enhancing endurance.

ERK1/2 Pathway Modulation:

ACE-031 indirectly modulates the MAPK/ERK1/2 signaling pathway, promoting muscle survival and inhibiting apoptosis. This contributes to its muscle-protective effects, especially under metabolic stress or during cachexia.

Bone Remodeling Regulation:

ACE-031 reduces osteoclastogenesis by decreasing RANKL activity and increasing osteoprotegerin expression. It also enhances osteoblast gene expression (Runx2, ALP), promoting bone formation and mineral density.