ACE-031

A recombinant fusion protein (~101 kDa) consisting of the extracellular domain of human activin receptor type IIB (ActRIIB) fused to the Fc portion of human IgG1. Not a traditional peptide — it is approximately 10× larger than IGF-1 LR3 and requires mammalian cell expression systems for proper folding and glycosylation. Developed by Acceleron Pharma (acquired by Merck in 2021).

ACE-031 functions as a soluble decoy receptor (ligand trap), binding myostatin, activin A/B, GDF-11, and other TGF-β superfamily ligands before they engage endogenous ActRIIB receptors. Phase 1 trials in healthy postmenopausal women demonstrated a 3.3% increase in lean mass from a single injection. A Phase 2 trial in ambulatory boys with Duchenne muscular dystrophy showed a 5.2% lean mass increase, but trials were permanently halted in 2013 due to vascular safety signals (epistaxis, telangiectasias, gum bleeding) caused by off-target inhibition of BMP9/BMP10 in the ALK1 endothelial signaling pathway.

Research chemical suppliers listing 'ACE-031' typically sell truncated peptide fragment analogs that are structurally distinct from the clinical-grade fusion protein.

ACE-031 is the only compound in this batch with controlled human clinical trial data. Attie et al. (2013) reported dose-dependent lean mass increases up to 3.3% from a single subcutaneous injection in 48 healthy postmenopausal women. Campbell et al. (2017) published results from the Phase 2 DMD trial showing 5.2% lean mass increase (P=0.015) and a trend toward improved 6-minute walk test (+12 m vs. -30 m placebo, P=0.06) in 24 steroid-treated boys.

Preclinical data showed 26-46% increases in individual muscle weights in mice after 28 days (Cadena et al., 2010). Trials were permanently halted due to BMP9/10-mediated vascular adverse events. Successor compounds ACE-2494 and ACE-083 also failed in clinical development. The ActRIIB decoy receptor approach remains stalled as of March 2026.