Side-by-side · Research reference
ACE-031vsDihexa
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-REVIEWED7/28 cited
ACE-031
ActRIIB-Fc Fusion · Phase 2 Halted
SQ · Weekly dosing investigated
Dihexa
Angiotensin IV Analogue · Pre-Clinical
Not established — animal studies only
01Mechanism of Action
Parameter
ACE-031
Dihexa
Primary target
Myostatin, GDF11, activin A — TGF-β superfamily ligands
c-Met receptor (HGF receptor tyrosine kinase)
Pathway
Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition
HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization
Downstream effect
Disinhibition of myogenic signaling, increased skeletal muscle mass and strength
Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models
Feedback intact?
—
—
Origin
Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025
Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015
Antibody development
—
—
02Dosage Protocols
Parameter
ACE-031
Dihexa
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
Pre-clinical / Rodent models
Half-life
Days to weeks (Fc-fusion typical kinetics)
IgG1-Fc domain confers extended circulation time.
—
Duration investigated
12–24 weeks (trial cut short)
—
Human dosing
—
Not established — no human trials
Animal studies
—
Mouse/rat models only — dosing not translatable to humans
Clinical status
—
No Phase 1, 2, or 3 trials published
04Side Effects & Safety
Parameter
ACE-031
Dihexa
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
—
Human safety data
—
None available — no human clinical trials
Theoretical c-Met risks
—
c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile
Pre-clinical tolerability
—
Not systematically reported in available studies
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
Dihexa
- ·Not approved for human use — research compound only
Relative Contraindications
ACE-031
- ·Coagulation disorders or anticoagulant use (epistaxis risk)
- ·Hereditary hemorrhagic telangiectasia (HHT) family history
- ·Cardiovascular disease (vascular remodeling effects unknown)
Dihexa
- ·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)
05Administration Protocol
Parameter
ACE-031
Dihexa
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.
No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.
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
Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.
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
—
4. Clinical trial route
Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.
—