Side-by-side · Research reference
ACE-031vsFOXO4-DRI
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 2HUMAN-REVIEWED10/44 cited
BAnimal-StrongHUMAN-REVIEWED12/45 cited
ACE-031
ActRIIB-Fc Fusion · Phase 2 Halted
SQ · Weekly dosing investigated
FOXO4-DRI
Senolytic Peptide · D-Retro-Inverso
SQ · Animal models only
01Mechanism of Action
Parameter
ACE-031
FOXO4-DRI
Primary target
Myostatin, GDF11, activin A — TGF-β superfamily ligands
FOXO4-p53 protein complex in senescent cellsBourgeois 2025Tripathi 2021
Pathway
Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition
FOXO4-DRI binds disordered p53 transactivation domain → displaces FOXO4 → nuclear p53 exclusion → p53-mediated apoptosis in senescent cells
Downstream effect
Disinhibition of myogenic signaling, increased skeletal muscle mass and strength
Selective apoptosis of senescent cells; clearance restores tissue homeostasisTripathi 2021Alameen 2026
Feedback intact?
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Origin
Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025
D-retro-inverso modification — inverted amino acid sequence, D-amino acids for protease resistance
Antibody development
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02Dosage Protocols
Parameter
ACE-031
FOXO4-DRI
Clinical dosing
Weekly or biweekly SQ injections (exact doses undisclosed pre-halt)
Phase 2 DMD trial protocol not fully published.
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Black market products
Variable purity; 12/14 tested products contained target protein plus contaminantsReichel 2025
SDS-PAGE revealed multiple protein bands; quality control absent.Reichel 2025
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Evidence basis
Phase 2 trial discontinued — incomplete dataset
Animal / mechanistic
Half-life
Days to weeks (Fc-fusion typical kinetics)
IgG1-Fc domain confers extended circulation time.
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Duration investigated
12–24 weeks (trial cut short)
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Animal dose (mouse)
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5 mg/kg
SQ injection, aged mouse model (testosterone restoration).
Frequency (animal)
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Variable — single or intermittent dosing
Protocol-dependent; no standardised regimen.
Human equivalent (theoretical)
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~0.4 mg/kg (28 mg / 70 kg adult)
Extrapolated using allometric scaling; no clinical validation.
Route
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SQ (animal)
No human route established.
Duration
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Weeks to months (animal studies)
Senescent cell clearance observed within weeks.
Clinical status
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No human trials completed
04Side Effects & Safety
Parameter
ACE-031
FOXO4-DRI
Epistaxis (nosebleeds)
Significant incidence in Phase 2 DMD trial — primary safety signal
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Telangiectasia
Dilated capillaries / spider veins observed
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Vascular abnormalities
Mechanism: ActRIIB/ALK1 pathway disruption affects vascular homeostasis
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Injection site reactions
Local erythema, induration (biologics class effect)
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Antibody development
Potential for anti-drug antibodies (Fc-fusion proteins); incidence not reported
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Black market contaminants
12/14 tested products contained multiple unidentified proteins alongside ACE-031Reichel 2025
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Pulmonary hypertension risk
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Senescent cell elimination promoted PH development/progression in rodent modelsBorn 2023
Context-dependent toxicity
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Beneficial effects may be tissue/context-specific; elimination not universally protectiveBorn 2023
Off-target apoptosis
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Theoretical risk of non-senescent cell apoptosis (selectivity not absolute)
Immune perturbation
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Senescent cells contribute to immune surveillance; clearance effects unknown
Human safety unknown
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No clinical trials — toxicity profile in humans not established
Absolute Contraindications
ACE-031
- ·History of vascular disorders (epistaxis, telangiectasia, HHT)
- ·Pregnancy (TGF-β pathway critical for fetal development)
- ·Active malignancy (myostatin inhibition may affect tumour growth)
- ·Use of non-pharmaceutical grade ACE-031 (contamination risk)Reichel 2025
FOXO4-DRI
- ·Pulmonary hypertension or vascular disease (preclinical evidence of harm)Born 2023
- ·Pregnancy / lactation (no safety data)
Relative Contraindications
ACE-031
- ·Coagulation disorders or anticoagulant use (epistaxis risk)
- ·Hereditary hemorrhagic telangiectasia (HHT) family history
- ·Cardiovascular disease (vascular remodeling effects unknown)
FOXO4-DRI
- ·Active malignancy (senescence as tumour suppressor mechanism)
- ·Wound healing / tissue repair (senescent cells involved in fibrosis resolution)
05Administration Protocol
Parameter
ACE-031
FOXO4-DRI
1. Pharmaceutical status
ACE-031 is not FDA-approved or commercially available. Phase 2 development was discontinued in 2011 due to safety concerns. Any ACE-031 on the black market is unregulated research chemical.
Subcutaneous injection used in rodent models. No human administration protocol exists.
2. Black market quality
12 of 14 tested black market ACE-031 products contained the target protein but also carried multiple unidentified protein contaminants detectable by SDS-PAGE. Two products contained no ACVR2B-immunoreactive material.Reichel 2025
Typically reconstituted in sterile saline or PBS for animal experiments. Stability data limited.
3. Detection in sport
ACE-031 is prohibited under WADA S4.3 (Myostatin Inhibitors). Gel electrophoresis and Western blotting using ACVR2B-specific antibodies can detect the ~58.4 kDa protein in biological samples.Reichel 2025
Variable — single bolus or intermittent dosing over weeks. No standardised human protocol.
4. Clinical trial route
Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.
No registered human trials. Commercialisation by Cleara Biotech (Netherlands) in development phase.
5. Safety monitoring (proposed)
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Would require cardiovascular assessment, pulmonary function, immune panel, tumour surveillance if human trials proceed.