Side-by-side · Research reference
ACE-031vsVIP
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
BPhase 3HUMAN-REVIEWED9/42 cited
ACE-031
ActRIIB-Fc Fusion · Phase 2 Halted
SQ · Weekly dosing investigated
VIP
Neuropeptide · VPAC1/VPAC2 Agonist · Emergency Use Authorization (COVID-19 ARDS)
IV infusion · Inhaled (investigational)Brown 2023Boesing 2022
01Mechanism of Action
Parameter
ACE-031
VIP
Primary target
Myostatin, GDF11, activin A — TGF-β superfamily ligands
VPAC1 and VPAC2 G-protein-coupled receptorsUdupa 2025
Pathway
Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition
VIP → VPAC1/VPAC2 activation → cAMP elevation → Pulmonary vasodilation + epithelial protection
Downstream effect
Disinhibition of myogenic signaling, increased skeletal muscle mass and strength
Anti-inflammatory cytokine modulation, alveolar-capillary membrane stabilization, pulmonary smooth muscle relaxation, reduced neutrophil infiltration
Feedback intact?
—
Yes — exogenous VIP acts as physiological agonist
Origin
Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025
Endogenous 28-amino-acid neuropeptide; synthetic analogue (aviptadil) identical to natural VIP
Antibody development
—
—
02Dosage Protocols
Parameter
ACE-031
VIP
Clinical dosing
Weekly or biweekly SQ injections (exact doses undisclosed pre-halt)
Phase 2 DMD trial protocol not fully published.
—
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
—
Evidence basis
Phase 2 trial discontinued — incomplete dataset
Phase 3 RCT (TESICO)Brown 2023
816-patient randomized controlled trial in COVID-19 ARDS.
Half-life
Days to weeks (Fc-fusion typical kinetics)
IgG1-Fc domain confers extended circulation time.
~2 minutes (plasma)
Rapid clearance necessitates continuous infusion.
Duration investigated
12–24 weeks (trial cut short)
—
Intravenous (ARDS protocol)
—
60–90 mcg/kg/day via continuous infusion
TESICO trial protocol for COVID-19 ARDS.
Inhaled (investigational)
—
Variable dosing under clinical trial protocolsBoesing 2022
Delivered via nebulizer for direct pulmonary deposition.
Treatment duration
—
3–14 days (acute ARDS)
Reconstitution
—
Lyophilized powder reconstituted with sterile diluent per protocol
04Side Effects & Safety
Parameter
ACE-031
VIP
Epistaxis (nosebleeds)
Significant incidence in Phase 2 DMD trial — primary safety signal
—
Telangiectasia
Dilated capillaries / spider veins observed
—
Vascular abnormalities
Mechanism: ActRIIB/ALK1 pathway disruption affects vascular homeostasis
—
Injection site reactions
Local erythema, induration (biologics class effect)
—
Antibody development
Potential for anti-drug antibodies (Fc-fusion proteins); incidence not reported
—
Black market contaminants
12/14 tested products contained multiple unidentified proteins alongside ACE-031Reichel 2025
—
Hypotension
—
Transient vasodilation-related blood pressure drop
Tachycardia
—
Reflex tachycardia secondary to vasodilation
Infusion site reactions
—
Erythema, phlebitis (IV administration)
GI symptoms
—
Nausea, diarrhea (VIP is endogenous GI peptide)
Overall tolerability
—
Well-tolerated in Phase 3 trials; adverse event profile comparable to placebo
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
VIP
- ·Known hypersensitivity to aviptadil or formulation components
Relative Contraindications
ACE-031
- ·Coagulation disorders or anticoagulant use (epistaxis risk)
- ·Hereditary hemorrhagic telangiectasia (HHT) family history
- ·Cardiovascular disease (vascular remodeling effects unknown)
VIP
- ·Severe hypotension or shock states (monitor blood pressure)
- ·Pregnancy — insufficient safety data
05Administration Protocol
Parameter
ACE-031
VIP
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.
Reconstitute lyophilized aviptadil powder with sterile diluent per manufacturer protocol. Inspect solution for particulates — should be clear and colorless.
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
Administer as continuous 12-hour intravenous infusion via central or peripheral line. Use infusion pump for precise dosing (60–90 mcg/kg/day divided over infusion duration).
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
Monitor blood pressure, heart rate, and oxygenation continuously during first infusion. Assess for hypotension and adjust infusion rate if needed.
4. Clinical trial route
Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.
Deliver via jet or mesh nebulizer per clinical trial protocol. Patient seated upright, normal tidal breathing for 10–15 minutes.
5. Storage
—
Store lyophilized powder at 2–8 °C, light-protected. Reconstituted solution: use immediately or within 24 hours if refrigerated.