Peptides›GH-stack›ACE-031

ACE-031

/ Recombinant human activin receptor type IIB extracellular domain — IgG1 Fc fusion protein

TIER 2 · TranslationalN = 0 · TESTING PENDINGMW 160000.00 g·mol⁻¹

ALIAS · ActRIIB-Fc · Soluble activin receptor IIB-Fc fusion · Acceleron ActRIIB

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · 160000.00CLASS · Recombinant human activin receptor type IIB extracellular domain — IgG1 Fc fusion proteinCATEGORY · GH-stack

Tier 2. Acceleron Pharma's ACE-031 reached Phase 2 in Duchenne muscular dystrophy before development was halted in 2013 due to non-muscle-related adverse events (epistaxis, telangiectasia, gum bleeding) consistent with off-target effects of ActRIIB ligand trapping (BMP9, BMP10).

§ B · Mechanism of action

ACE-031 is a soluble decoy receptor consisting of the extracellular domain of human activin receptor IIB (ActRIIB) fused to an IgG1 Fc tail. It sequesters circulating myostatin, activin A, GDF11, BMP9, BMP10, and related TGF-β superfamily ligands, preventing their engagement of cell-surface ActRIIB on muscle and other tissues. The intended muscle-anabolic effect derives from blocking myostatin signalling; the unintended off-target engagement of vascular/endothelial BMP9-BMP10 axes drove the safety signal that halted development.

§ C · Human clinical evidence

Tier 2. Phase 1 single-ascending-dose data in healthy postmenopausal women showed dose-dependent lean mass increases. A Phase 2 trial in DMD boys was terminated for safety. No Phase 3 trials. Acceleron pivoted to luspatercept (ActRIIB-IgG1Fc with ligand-binding domain modifications) which is FDA-approved for myelodysplastic syndrome anaemia — a different molecule, different indication.

§ D · Primary literature

PubMed23169607Attie KM et al. — A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers · Muscle & Nerve · human-phase-1Single SC ACE-031 doses produced dose-dependent increases in serum follistatin and lean body mass in healthy postmenopausal women; established initial human PK/PD.Limitations: Single-dose study in healthy women; not a disease population.2013

PubMed27462804Campbell C et al. — Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial · Muscle & Nerve · human-phase-2Phase 2 in ambulatory DMD boys was terminated early due to vascular adverse events (epistaxis, telangiectasia); no efficacy on 6-minute walk distance was demonstrated in the truncated dataset.Limitations: Trial terminated early; small n; safety signal precluded full efficacy assessment.2017

§ F · Safety signal

Halted in DMD due to recurrent epistaxis, gingival bleeding, and cutaneous telangiectasia thought to reflect blockade of BMP9/BMP10 vascular signalling. The Acceleron program produced clear evidence that broad-spectrum ActRIIB ligand trapping has unacceptable off-target effects.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The ACE-031 safety signal is a load-bearing reason that subsequent myostatin programs (e.g. domagrozumab, taldefgrobep, garetosmab) used more selective binding designs (anti-myostatin antibodies, refined receptor traps). Read-through to vendor-sold 'myostatin inhibitor' research peptides is limited — none are pharmacologically equivalent to ACE-031.