Side-by-side · Research reference

ACE-031vsCortagen

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-MechanisticHUMAN-REVIEWED11/35 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

Cortagen

Bioregulatory Tetrapeptide · Khavinson-School

TetrapeptideStructure

↓ LPO productsAntioxidant effectKozina 2007

AnimalEvidence level

Injectable · Animal models

01Mechanism of Action

Parameter

ACE-031

Cortagen

Primary target

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

Cerebral cortex tissue — molecular targets under investigation

Pathway

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

Antioxidant pathway modulation — suppression of LPO cascade, reduction of protein oxidative modificationKozina 2007

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Decreased lipid peroxidation products, reduced oxidative protein damage, altered gene expression in cardiac tissueKozina 2007 Anisimov 2004

Feedback intact?

—

Origin

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

Synthetic tetrapeptide derived from amino acid analysis of natural brain cortex peptide preparation CortexinAnisimov 2004

Antibody development

—

02Dosage Protocols

Parameter

ACE-031

Cortagen

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 mechanistic studies

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

—

Duration investigated

12–24 weeks (trial cut short)

—

Animal model dose (rat)

—

Injection protocol (dose not specified in abstracts)

Multiple injections over study period.

Avian model dose (chicken)

—

40-day injection courseKuznik 2008

Compared to epithalon in hypophysectomized and aged birds.

Human peripheral nerve study

—

Therapeutic course (protocol details not provided)

Posttraumatic recovery context — reference cited but not detailed.

Route

—

Injectable (inferred from animal protocols)

04Side Effects & Safety

Parameter

ACE-031

Cortagen

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

—

Antioxidant suppression

—

Suppression of antioxidant activity noted alongside LPO reductionKozina 2007

Mechanism unclear — possible homeostatic adaptation.

Immune/hemostasis effects

—

No effect on immunity or hemostasis parameters in avian hypophysectomy model (unlike epithalon)Kuznik 2008

Epithalon reversed deficits; cortagen did not.

Human safety data

—

No adverse events reported in peripheral nerve recovery context

Limited detail in available abstracts.

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

Cortagen

—

Relative Contraindications

ACE-031

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

Cortagen

—

05Administration Protocol

Parameter

ACE-031

Cortagen

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 lyophilised peptide with bacteriostatic water per supplier protocol. Exact volumes depend on concentration supplied.

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

Subcutaneous injection typical for bioregulatory peptides — abdomen or thigh. 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

Animal protocols used repeated dosing over weeks. Human timing not established — evening administration common in Khavinson tradition.

4. Clinical trial route

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

Lyophilised: refrigerate or freeze per supplier. Reconstituted: refrigerate 2–8 °C, use within guideline window.