Side-by-side · Research reference
ACE-031vsDermorphin
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-REVIEWED20/47 cited
ACE-031
ActRIIB-Fc Fusion · Phase 2 Halted
SQ · Weekly dosing investigated
Dermorphin
Opioid Peptide · μ-Receptor Agonist · Research Only
Research only · ICV / SC (animal models)
01Mechanism of Action
Parameter
ACE-031
Dermorphin
Primary target
Myostatin, GDF11, activin A — TGF-β superfamily ligands
μ-opioid receptors (central and peripheral)Negri 1992Steel 2014
Pathway
Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition
μ-receptor activation → G-protein coupling → adenylyl cyclase inhibition → neuronal hyperpolarization
Downstream effect
Disinhibition of myogenic signaling, increased skeletal muscle mass and strength
Potent analgesia, reduced nociceptive signaling, opioid-mediated CNS and peripheral effects
Feedback intact?
—
N/A — exogenous opioid agonist
Origin
Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025
Phyllomedusa sauvagei and P. bicolor frog skin — gene-encoded with natural D-amino acid incorporationAmiche 1998Mignogna 1992
02Dosage Protocols
Parameter
ACE-031
Dermorphin
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
Animal studies · In vitro assays
Half-life
Days to weeks (Fc-fusion typical kinetics)
IgG1-Fc domain confers extended circulation time.
—
Duration investigated
12–24 weeks (trial cut short)
—
Legal status
—
Controlled substance in many jurisdictions · Research only
Not approved for human use.
Animal research (ICV)
—
Low nanomolar to picomolar range
Intracerebroventricular administration in rodent models.
Detection limit (doping)
—
5 pg/mL in equine plasma/urineSteel 2014
High-throughput LC-MS/MS screen developed for racing industry.
Duration of action
—
10–120 minutes (dose-dependent, intrathecal)
Human toxicity
—
Kambô ritual (P. bicolor skin) — violent emesis, vasodilation, fluid shifts, ADH dysregulationTran 2025
04Side Effects & Safety
Parameter
ACE-031
Dermorphin
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
—
Opioid effects
—
Respiratory depression, sedation, euphoria, tolerance, dependence risk
Kambô ritual toxicity
—
Violent emesis, vasodilation, profound fluid shifts, hyponatremia, ADH dysregulation, brain death (case report)Tran 2025
Receptor selectivity caveat
—
Two μ-receptor subtypes — differential behavioral effects (analgesia vs. catalepsy)Negri 1992
Proteolytic stability
—
Tyr³-Pro⁶ bond relatively unstable; endogenous enzymes may produce tetrapeptide fragmentsCucumel 1996
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
Dermorphin
- ·Human use — not approved by any regulatory authority
- ·Controlled substance status — possession illegal in many jurisdictions
- ·Known opioid hypersensitivity or respiratory compromise
Relative Contraindications
ACE-031
- ·Coagulation disorders or anticoagulant use (epistaxis risk)
- ·Hereditary hemorrhagic telangiectasia (HHT) family history
- ·Cardiovascular disease (vascular remodeling effects unknown)
Dermorphin
- ·Any context outside approved animal research protocols
- ·CNS depressant co-administration
05Administration Protocol
Parameter
ACE-031
Dermorphin
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.
Dermorphin is a controlled substance in many jurisdictions and is not approved for human use. Possession, synthesis, or distribution may be illegal. Use is restricted to licensed research settings under institutional review.
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
In rodent models, intracerebroventricular (ICV) or intrathecal injection is used at nanomolar to picomolar concentrations. Subcutaneous administration also documented. All protocols require IACUC approval.
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
High-throughput LC-MS/MS screens developed for anti-doping programs detect dermorphin and 17 related peptides in equine and human urine/plasma at limits as low as 5 pg/mL.Steel 2014
4. Clinical trial route
Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.
Application of Phyllomedusa bicolor skin secretions to superficial burns. Not recommended — associated with severe toxicity including violent emesis, hyponatremia, and documented case of brain death.Tran 2025