Side-by-side · Research reference

ACE-031vsMelanotan-II

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 1HUMAN-REVIEWED9/43 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

Melanotan-II

MC1R + MC4R agonist · Tanning + sexual response

0.25–1.0 mgPer doseDorr 1996

Phase 1Evidence levelDorr 1996

~1 hrHalf-life

SQ · Abdomen · Loading 5–7 days, then maintenance

01Mechanism of Action

Parameter

ACE-031

Melanotan-II

Primary target

Myostatin, GDF11, activin A — TGF-β superfamily ligands

MC1R (skin) + MC3R + MC4R (CNS sexual / appetite)Dorr 1996

Pathway

Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition

MC1R agonism → melanocyte tyrosinase → eumelanin synthesis. MC4R → autonomic sexual arousal centresDorr 1996 Simerly 2023

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Skin darkening, photo-protection, increased sexual desire / spontaneous erectionDorr 1996

Feedback intact?

—

Origin

Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025

Cyclic 7-AA modified α-MSH analog; designed at University of ArizonaDorr 1996

Antibody development

—

02Dosage Protocols

Parameter

ACE-031

Melanotan-II

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 1 + anecdotalDorr 1996

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

~1 hour plasma; effects on melanocytes persist days

Duration investigated

12–24 weeks (trial cut short)

—

Loading phase

—

0.25–0.5 mg/day SQ × 5–7 daysDorr 1996

Builds up to visible tan.

Maintenance

—

0.5–1.0 mg 1–2×/week

After visible tan develops; supports with UV exposure.

Frequency

—

Daily during loading; 1–2× per week maintenance

Lower / starter dose

—

0.1 mg / day

Conservative starter — assess tolerability for nausea.

Duration

—

8–12 weeks per cycle

Reconstitution

—

Bacteriostatic water; protect from light

Timing

—

Evening preferred (24h tan-development cycle)

04Side Effects & Safety

Parameter

ACE-031

Melanotan-II

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

—

Nausea

—

Common, especially loading phase

Flushing

—

Common transient

Spontaneous erection

—

Common in men — MC4R cross-effectDorr 1996

Increased mole / freckle pigmentation

—

Existing moles darken; new lesions possible

Melanoma risk

—

Theoretical concern — increased melanocyte activity; CAUTION in melanoma history

Appetite suppression

—

MC4R-mediated; mild

Pregnancy / OB

—

Contraindicated

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

Melanotan-II

·History of melanoma or atypical mole syndrome
·Pregnancy / breastfeeding
·Active uncontrolled hypertension

Relative Contraindications

ACE-031

·Coagulation disorders or anticoagulant use (epistaxis risk)
·Hereditary hemorrhagic telangiectasia (HHT) family history
·Cardiovascular disease (vascular remodeling effects unknown)

Melanotan-II

·Significant freckling / dysplastic nevus
·Personal or family melanoma history

05Administration Protocol

Parameter

ACE-031

Melanotan-II

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.

Add 2 mL bacteriostatic water to 10 mg vial → 5 mg/mL = 500 mcg per 0.1 mL. Light-protected.

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

SQ — abdomen. Rotate sites.

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

Evening preferred. UV exposure (sunlight or tanning bed) helps develop tan.

4. Clinical trial route

Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.

Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.

5. Needle

—

29–31G insulin syringe.