Side-by-side · Research reference

ACE-031vsPancragen

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-REVIEWED23/39 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

Pancragen

Bioregulatory Tetrapeptide · Khavinson School

50 μgPrimate doseGoncharova 2014

10 daysTreatment cycleGoncharova 2015

3+ weeksEffect persistenceGoncharova 2014

IM · 10-day cycleGoncharova 2014

01Mechanism of Action

Parameter

ACE-031

Pancragen

Primary target

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

Pancreatic acinar and islet cell differentiation pathwaysKhavinson 2013

Pathway

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

Transcription factor activation → Pdx1/Pax6/Pax4/Ptf1a/Foxa2/NKx2.2 upregulation → Cell differentiationKhavinson 2013

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Enhanced pancreatic beta-cell function, normalized insulin/C-peptide dynamics, improved glucose clearanceGoncharova 2014

Feedback intact?

—

Yes — preserves physiological glucose-insulin response

Origin

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

Synthetic tetrapeptide derived from pancreatic tissue extracts (Khavinson bioregulator methodology)

Antibody development

—

02Dosage Protocols

Parameter

ACE-031

Pancragen

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

Non-human primate RCT, in vitro cell cultureGoncharova 2015 Khavinson 2013

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

—

Duration investigated

12–24 weeks (trial cut short)

—

Primate dose (rhesus macaque)

—

50 μg / animal / dayGoncharova 2014

20–25-year-old females, 10-day IM protocol.

Effective concentration (in vitro)

—

0.05 ng/mLZakutskiĭ 2006

Organotypic tissue culture, both young and aged rat explants.

Route

—

IntramuscularGoncharova 2015

Frequency

—

Once daily for 10 daysGoncharova 2014

Treatment cycle

—

10-day course, effects persist 3+ weeks post-withdrawalGoncharova 2014

Diabetes model

—

STZ-induced diabetes (rat)

Evaluated via metabolic markers characterizing apoptosis.

04Side Effects & Safety

Parameter

ACE-031

Pancragen

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

—

Reported adverse events

—

None documented in primate studies

Tolerability

—

Well-tolerated in aged rhesus monkeys (n=9)Goncharova 2015

Human safety data

—

No published human trials; clinical use limited to Russian gerontology protocols

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

Pancragen

—

Relative Contraindications

ACE-031

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

Pancragen

·Active pancreatic malignancy (proliferation marker upregulation)

05Administration Protocol

Parameter

ACE-031

Pancragen

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.

Lyophilised tetrapeptide reconstituted in sterile saline or water per manufacturer protocol. Concentration not specified in literature.

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

Intramuscular injection. Primate studies used daily IM dosing for 10 consecutive days.Goncharova 2015

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

No specific timing constraints documented. Administered once daily in primate protocols.

4. Clinical trial route

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

10-day treatment course. Restorative effects on pancreatic function persist for at least 3 weeks post-discontinuation.Goncharova 2014