Side-by-side · Research reference

ACE-031vsARA 290

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 2HUMAN-REVIEWED17/59 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

ARA 290

EPO-Derived Peptide · Innate Repair Receptor Agonist

4 mgDaily doseBrines 2015 Culver 2017

28 daysPhase 2 durationCulver 2017

Non-erythropoieticSafety profileBrines 2015 Liu 2014

SQ · DailyBrines 2015 Culver 2017

01Mechanism of Action

Parameter

ACE-031

ARA 290

Primary target

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

Innate repair receptor (EPO receptor / CD131 heterodimer)

Pathway

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

EPO/CD131 → JAK2 activation → PI3K/AKT, MAPK signaling → anti-inflammatory, anti-apoptotic cascades

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Tissue protection, nerve fiber regeneration, suppression of inflammatory macrophage activation, altered T-cell differentiation (↑Treg, ↑Th2, ↓Th1)Liu 2014 Culver 2017

Feedback intact?

—

N/A — does not interact with hematopoietic EPO receptorLiu 2014

Origin

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

11-amino-acid sequence from EPO helix B, engineered to eliminate hematopoietic activity while retaining tissue-protective properties

Antibody development

—

Not reported in clinical trials

02Dosage Protocols

Parameter

ACE-031

ARA 290

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 2 RCTsCulver 2017 Brines 2015

64-subject sarcoidosis trial, type 2 diabetes trial.

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

—

Duration investigated

12–24 weeks (trial cut short)

—

Standard dose (Phase 2)

—

4 mg / dayBrines 2015 Culver 2017

Sarcoidosis SFN and diabetic neuropathy trials.

Frequency

—

Once daily

Self-administered subcutaneously.

Duration

—

28 days (Phase 2)Culver 2017

Corneal nerve improvements observed by day 28.

Route

—

SubcutaneousBrines 2015

Timing

—

Any time of day

No circadian dependence reported.

03Metabolic / Fat Loss Evidence

Parameter

ACE-031

ARA 290

Primary effect

—

Improved metabolic control (HbA1c, fasting glucose)Brines 2015

Secondary to neuropathy treatment; direct lipolytic effects not established.

HbA1c

—

Significant reduction vs placebo

Observed in type 2 diabetes + neuropathy trial.

Fasting glucose

—

Improved in ARA 290 group

Body composition

—

Not directly quantified

Fat loss not a primary endpoint; metabolic improvements may reflect insulin sensitivity.

04Side Effects & Safety

Parameter

ACE-031

ARA 290

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

—

Injection site reaction

—

Mild, transient

Hematopoiesis

—

None — non-erythropoietic

Distinguishes ARA 290 from native EPO.

Cardiovascular

—

No thrombotic events or hypertension reported

Immunogenicity

—

No antibody formation reported

Tolerability

—

Well-tolerated in Phase 2 trialsCulver 2017 Brines 2015

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

ARA 290

·Hypersensitivity to ARA 290

Relative Contraindications

ACE-031

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

ARA 290

·Active malignancy (theoretical EPO-axis concern; not observed in trials)

05Administration Protocol

Parameter

ACE-031

ARA 290

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 powder per manufacturer instructions. Use sterile technique.

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 — abdomen, thigh, or upper arm. Rotate sites to avoid lipohypertrophy.

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

Once daily, any time of day. Self-administered in Phase 2 trials.Brines 2015

4. Clinical trial route

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

4 mg daily for 28 days (Phase 2 protocol). Duration for chronic use not established.Culver 2017

5. Storage

—

Lyophilised: store at controlled room temperature. Reconstituted: refrigerate, use within specified timeframe.

06Stack Synergy

ACE-031

— no documented stacks

ARA 290

+ BPC-157

Moderate

View BPC-157 →

ARA 290 targets the innate repair receptor (EPO/CD131) for nerve regeneration and anti-inflammatory signaling, while BPC-157 promotes angiogenesis and tissue repair through distinct mechanisms (likely involving VEGF, growth hormone receptor pathways). Combined, they may address both neuroinflammation and structural tissue repair in neuropathy or injury models. No direct clinical data; mechanistic overlap in tissue protection.

ARA 290: 4 mg SQ · daily
BPC-157: 250–500 mcg SQ · daily
Frequency: Once daily, same or separate injections
Primary benefit: Nerve regeneration, pain reduction, tissue healing