ACE-031

ACE-031 is an engineered biologic developed by Acceleron Pharma (later in partnership with Shire) consisting of the extracellular, ligand-binding domain of the human activin receptor type IIB (ActRIIB) fused to the Fc portion of human immunoglobulin G1 (IgG1). At Verified Peptides, we classify this as a large fusion protein rather than a short synthetic peptide — like Follistatin 344, also built on this site, ACE-031 is a full biologic-scale molecule, not a small oligopeptide.

We want to flag a specific data-quality issue directly: several commercial vendor sites list a CAS registry number (1621169-52-5) and a small-molecule-style formula (C133H227N43O33, implying a molecular weight of roughly 2,956.5 g/mol) for ACE-031. These figures are inconsistent with ACE-031's well-documented identity as an approximately 57-90 kDa homodimeric fusion protein (molecular weight varies by source depending on whether the monomer, apparent SDS-PAGE weight, or glycosylated homodimer is being described) — a discrepancy of roughly 20 to 30-fold. We believe this reflects a data-entry error propagating across vendor sites (likely an unrelated compound's identifiers mistakenly attached to ACE-031 listings), and we are not repeating those specific figures here. Researchers should treat any single, simple CAS/small-molecule-formula listing for a fusion protein of this scale with real skepticism.

ACE-031's actual composition — the ActRIIB extracellular domain (residues 1-117 of the mature receptor) joined to an IgG1 Fc domain — reflects a well-established biologic engineering strategy (an "Fc-fusion" or "receptor trap"), the same general design approach used in several approved drugs across other disease areas, where fusing a receptor's ligand-binding domain to an antibody Fc region both confers a freely circulating, decoy-receptor function and extends plasma half-life relative to the receptor domain alone.

This Fc-fusion "receptor trap" strategy is the same general engineering approach behind several genuinely approved drugs in other therapeutic areas, such as etanercept (a TNF receptor-Fc fusion used for rheumatoid arthritis and other inflammatory conditions) and aflibercept (a VEGF/PlGF receptor-Fc fusion used in ophthalmology and oncology) — demonstrating that the underlying construction strategy behind ACE-031 is a well-validated biologic engineering approach, even though ACE-031 itself was ultimately discontinued for reasons specific to the ActRIIB receptor's broader ligand-binding profile rather than any flaw in the Fc-fusion strategy generally.

At Verified Peptides, we think ACE-031 is one of the more instructive compounds in this catalog precisely because of how its human clinical trial program actually ended. Acceleron completed a Phase 1 trial in Duchenne muscular dystrophy (DMD) patients in 2008-2009, in which single ascending doses over 29 days produced a 3.5% increase in muscle volume compared to 0.2% in placebo patients — a real, measurable early signal. The FDA subsequently granted ACE-031 both Orphan Drug and Fast Track designations for DMD in 2010, reflecting genuine regulatory recognition of its potential at that stage.

The pivotal Phase 2 trial (Campbell et al., Muscle & Nerve, 2017, PMID 27462804) was a randomized, double-blind, placebo-controlled, multiple ascending-dose study in ambulatory DMD boys, with ACE-031 administered subcutaneously every 2-4 weeks. The published results describe a trend toward maintained 6-minute walk test distance in ACE-031-treated groups compared to a decline in the placebo group, along with trends toward increased lean body mass and bone mineral density. We want to be precise about the word "trend" here: the trial was stopped early, after the second dosing regimen, due to safety concerns (epistaxis and telangiectasias), which limited the statistical power available to confirm these trends as definitive efficacy findings.

Acceleron and Shire formally discontinued the ACE-031 program in 2013, concluding their collaboration on the molecule and related compounds. This is an honest, important part of ACE-031's story: it is not a compound with an unresolved or ongoing development pathway toward approval — it is a discontinued clinical candidate with a real, disclosed safety-driven stopping point, now understood mechanistically (BMP9/vascular pathway inhibition) rather than being an unexplained failure.

The subsequent 2026 marmoset study (PMID 41686840) demonstrates that legitimate scientific interest in ACE-031 as a research tool for studying ActRIIB/myostatin pathway biology has continued well past the clinical program's discontinuation, even though no renewed human therapeutic development has followed. At Verified Peptides, we sell research-grade ACE-031 exclusively for laboratory research, and we think its combination of real early human efficacy signals, a well-documented and mechanistically explained safety-driven discontinuation, and continued legitimate preclinical research interest makes it a genuinely well-characterized, if ultimately unsuccessful, clinical candidate.

ACE-031's discontinuation is one of the more thoroughly explained safety-driven program terminations in the myostatin-pathway research space: rather than remaining an unexplained clinical failure, subsequent research specifically identified BMP9 (bone morphogenetic protein 9) inhibition — a consequence of ACE-031's broad ActRIIB-blocking activity rather than a myostatin-specific effect — as the likely mechanistic driver of the vascular side effects (epistaxis, telangiectasias) observed in treated DMD patients. BMP9 signaling through ALK1 is independently well-established as important for maintaining vascular endothelial integrity, providing a coherent mechanistic explanation rather than an unexplained safety signal.

This mechanistic understanding has directly informed the design of subsequent myostatin-pathway drug candidates: later-generation molecules in this space have been engineered to more selectively target myostatin and activin A while sparing BMP9 binding, specifically to avoid reproducing ACE-031's vascular side-effect profile — making ACE-031 a genuinely instructive negative example that shaped the broader field's subsequent drug-design strategy, not merely an abandoned compound.

Despite the clinical program's 2011 discontinuation and Acceleron/Shire's 2013 formal collaboration wind-down, ACE-031 has continued to appear in legitimate preclinical research as a well-characterized tool compound for studying ActRIIB pathway biology, exemplified by the 2026 marmoset study describing detailed muscle fiber and force measurements — indicating the molecule's ongoing scientific utility as a research reagent even without any active therapeutic development program behind it.

ACE-031 received both FDA Orphan Drug and Fast Track designations for Duchenne muscular dystrophy in 2010, both of which are formal regulatory recognitions of a drug candidate's potential importance for a serious, underserved condition — these designations do not constitute approval and lapsed in relevance once clinical development was discontinued, but they are a genuine part of the compound's documented regulatory history.

At Verified Peptides, we require independent third-party analytical verification — including SDS-PAGE, size-exclusion chromatography, and mass spectrometry identity confirmation appropriate for a protein of this size and complexity — for every batch of research-grade ACE-031 we offer, with a Certificate of Analysis (COA) available for each lot. As an engineered Fc-fusion protein requiring proper folding, glycosylation, and homodimeric assembly, ACE-031 demands considerably more sophisticated recombinant expression and purification than the short synthetic peptides that make up most of this catalog.

We source exclusively from manufacturers operating under Good Manufacturing Practice (GMP)-aligned quality systems, and every lot is independently verified rather than accepted solely on a supplier's internal documentation. Given the CAS/molecular-formula inconsistency we identified across vendor sources, researchers should be especially careful to request direct analytical confirmation (mass spectrometry, size-exclusion chromatography for dimeric assembly) rather than relying on a listed CAS number to confirm identity.

Lyophilized ACE-031 should be stored at -20°C or colder, protected from light and moisture. As a larger, more structurally complex Fc-fusion protein than the short peptides elsewhere in this catalog, ACE-031 may be more sensitive to freeze-thaw-induced aggregation or structural disruption, and researchers should follow lot-specific handling guidance closely. At Verified Peptides, we ship lyophilized material with appropriate cold-chain packaging to preserve stability in transit.

Once reconstituted, ACE-031 solution should be stored refrigerated at 2–8°C and used within the timeframe indicated on the product's documentation, or aliquoted and stored frozen for longer-term storage, avoiding repeated freeze-thaw cycles. Proper maintenance of the homodimeric Fc-fusion structure is important for retaining biological activity, making careful handling more consequential for this compound than for simple short peptides.