Side-by-side · Research reference

ACE-031vsPT-141

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

BFDA-ApprovedHUMAN-REVIEWED13/41 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

PT-141

MC4R Agonist · FDA-Approved (HSDD)

1.75 mgPer doseVYLEESI (bremelanotide injecti 2019

Pre-sexTimingVYLEESI (bremelanotide injecti 2019

~2.7 hrHalf-lifeVYLEESI (bremelanotide injecti 2019

SQ · Abdomen / thigh · ≥45 min before sex

01Mechanism of Action

Parameter

ACE-031

PT-141

Primary target

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

Melanocortin-4 receptor (MC4R) in hypothalamusSimerly 2023 VYLEESI (bremelanotide injecti 2019

Pathway

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

MC4R agonism in paraventricular nucleus → autonomic + neuroendocrine sexual arousal pathwaysSimerly 2023

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Increased sexual desire and arousal; central rather than peripheral mechanismClayton 2015

Feedback intact?

—

Origin

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

Cyclic 7-AA peptide derived from α-MSH (agonist Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-OH cyclic)VYLEESI (bremelanotide injecti 2019

Antibody development

—

02Dosage Protocols

Parameter

ACE-031

PT-141

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

FDA-approved (HSDD pre-menopausal women)VYLEESI (bremelanotide injecti 2019 Clayton 2015

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

~2.7 hrVYLEESI (bremelanotide injecti 2019

Duration investigated

12–24 weeks (trial cut short)

—

Standard dose

—

1.75 mg SQVYLEESI (bremelanotide injecti 2019

Single dose ≥45 min before anticipated sexual activity. Max 1 dose / 24 hr.

Frequency

—

PRN, max 8 doses / month

Lower / starter dose

—

1 mg (off-label)

Duration

—

PRN; reassess if no benefit after 8 doses

Reconstitution

—

Pre-filled commercial pen (Vyleesi). Research vial: bacteriostatic water.

Timing

—

≥45 min before sexual activity

04Side Effects & Safety

Parameter

ACE-031

PT-141

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 (~40%); often transientVYLEESI (bremelanotide injecti 2019

Flushing

—

Common, transient

Injection site reaction

—

Erythema, mild pain

Headache

—

Common

Hyperpigmentation (focal)

—

Rare focal skin darkening; reversible after discontinuationVYLEESI (bremelanotide injecti 2019

Hypertension (transient)

—

Mean ↑6 mmHg systolic peaking ~4 h post-dose; resolves within 12 hVYLEESI (bremelanotide injecti 2019

Pregnancy / OB

—

Contraindicated

Cardiovascular disease

—

Use caution; transient BP rise

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

PT-141

·Uncontrolled hypertension
·Known cardiovascular disease (caution)
·Pregnancy

Relative Contraindications

ACE-031

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

PT-141

·Pre-existing hyperpigmentation disorders
·MC4R-pathway-dependent psychiatric conditions

05Administration Protocol

Parameter

ACE-031

PT-141

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.

Vyleesi: pre-filled auto-injector. Research vial: 2 mL bacteriostatic water per 10 mg → 5 mg/mL.

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 or thigh.

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

≥45 min before sexual activity for peak effect. Effect persists ~6–8 h.

4. Clinical trial route

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

Vyleesi: room temp ≤30 °C. Research vial: refrigerate after reconstitution.

5. Needle

—

Auto-injector (Vyleesi) or 29–31G, 4–8 mm insulin syringe.