ACE-031 (research generic name: ramatercept) is a soluble activin receptor type IIB–IgG1 Fc fusion protein — an "ActRIIB-Fc" decoy receptor. Although it is grouped with research peptides, it is technically a recombinant biologic (~110 kDa fusion protein), not a synthetic peptide. ChEMBL: CHEMBL2108674; highest clinical phase reached: 2.
Class
Myostatin/activin inhibitor — a soluble ActRIIB-IgG1 Fc fusion protein (decoy receptor). Single compound.
Mechanism
ACE-031 is the extracellular domain of the activin receptor type IIB (ActRIIB) fused to the Fc region of human IgG1. It works as a soluble decoy: it binds and sequesters ActRIIB ligands — myostatin (GDF-8), activin A, and GDF-11 — before they can reach the membrane-bound receptor. Because myostatin is a negative regulator of skeletal muscle, trapping it de-represses muscle growth, producing gains in muscle mass and strength. The same ligand family also influences bone turnover (research showed reduced resorption and increased bone-formation markers). Critically, ActRIIB ligands also help regulate the vasculature — and off-target inhibition of those ligands is the mechanistic basis for the program's defining safety problem.
Research summary
ACE-031 is unusually well-documented for a research compound, with real registered human-trial data rather than animal work alone:
- Preclinical / non-human primate: a 2025–26 study in the common marmoset (PLOS One; also bioRxiv/PubMed) confirmed increased muscle mass and strength in a non-human primate, extending earlier rodent (RAP-031 surrogate) findings.
- Phase 1 (NCT00755638, NCT00952887; healthy postmenopausal women; Attie et al. 2013, Muscle & Nerve): the trial reported increases in lean/thigh muscle mass plus favorable bone-marker shifts. Even at this stage, notable adverse events included dilated blood vessels and nosebleeds.
- Phase 2 (NCT01099761; ambulatory steroid-treated boys with Duchenne muscular dystrophy; Campbell et al. 2017, Muscle & Nerve): escalating dose vs placebo. The trial was stopped early and the open-label extension (NCT01239758) was terminated on preliminary safety grounds. Because of the early halt, efficacy was never established.
Human clinical trial data
In the phase 1 single ascending-dose study by Attie and colleagues (2012), 48 healthy postmenopausal women were randomized to receive a single dose of ACE-031, at one of several ascending dose levels, or placebo (3:1) (PubMed). In the randomized, placebo-controlled trial by Campbell and colleagues (2016) in boys with Duchenne muscular dystrophy, ACE-031 was given repeatedly in an ascending-dose design; the study was stopped after the second dosing regimen (PubMed). These describe what was studied in registered trials; ACE-031 was never approved and no label exists.
Clinical / safety context
Development was discontinued (~2013) and ACE-031 was never approved for any indication. The defining finding of the whole program is a safety signal: off-target inhibition of vascular-regulating ligands caused telangiectasia (spider veins), epistaxis (nosebleeds), and gum bleeding. This is the single most important thing the research record establishes about the compound.
Evidence quality — Moderate (safety-weighted)
Far better documented than most research peptides (multiple registered human trials plus recent non-human-primate data), but the human studies were small, Phase 2 was halted, efficacy was never proven, and there is no long-term safety data. The strongest, most actionable conclusion the literature supports is the vascular safety risk — not a muscle-growth efficacy claim.
Notes
ACE-031 is a recombinant Fc-fusion protein, not a synthetic peptide — it behaves like a biologic (large, cell-culture produced, long half-life). "ActRIIB-Fc" and "ramatercept" refer to the same molecule; do not confuse it with luspatercept or sotatercept. Expect it supplied as a lyophilized research protein.