ARA-290

Quick Facts

• Full Name: ARA-290 (Cibinetide)
• Aliases: Cibinetide, Innate Repair Receptor (IRR) agonist
• Category: Immune Health / Neuroprotection / Anti-Inflammatory / Neuropathic Pain
• Type: 11-amino-acid helix B surface peptide of erythropoietin (EPO); non-erythropoietic EPO mimic
• Molecular Weight: ~1.2 kDa
• Administration: Subcutaneous / Intravenous
• Typical Dose: 4 mg/day SubQ (clinical trial dose) or 2–4 mg 3x/week
• Half-Life: ~24 hours (longer than EPO)
• Status: Research Only; Phase II/III trials ongoing (sarcoidosis, diabetic neuropathy)
• WADA Status: Prohibited (S2 — EPO mimetics)

What It Does

ARA-290 is a peptide derived from the "helix B" surface region of erythropoietin (EPO) that selectively activates the Innate Repair Receptor (IRR) — a heterodimer of EPO receptor + beta-common receptor — without activating the classical EPO receptor responsible for red blood cell production. This separation of activity gives ARA-290 the tissue-protective, anti-inflammatory, and neuroprotective benefits of EPO without hematological risks (thrombosis, erythrocytosis). Phase II trials in sarcoidosis-associated small fiber neuropathy showed significant pain reduction and nerve fiber regeneration.

Mechanism of Action

1. IRR (Innate Repair Receptor) agonism: Binds EPO receptor + beta-common receptor heterodimer → activates JAK2/STAT3, PI3K/Akt, MAPK/ERK → tissue protection and repair
2. Non-erythropoietic: Does not stimulate classical homodimeric EPO receptor → no red blood cell production, no thrombosis risk
3. Neuroprotection and nerve regeneration: Activates IRR on Schwann cells and neurons → promotes nerve fiber regeneration (small fiber neuropathy reversal in human trials)
4. Anti-inflammatory: Suppresses NF-κB → reduces TNF-α, IL-1β, IL-6; promotes M2 macrophage polarization
5. Cytoprotection: Anti-apoptotic signaling in neurons, cardiomyocytes, renal tubular cells
6. Pain modulation: Direct effects on nociceptors via IRR activation → neuropathic pain reduction

Dosing Protocols

Clinical Trial Protocol (Sarcoidosis / Neuropathy)

• Dose: 4 mg SubQ daily for 28 days
• Observed: Significant improvement in neuropathic pain scores and small fiber density

Research Protocol

• Dose: 2–4 mg SubQ
• Frequency: Daily or 3x per week
• Duration: 4–8 week cycles
• Source: The Peptides Bible, Brines et al. trials

Stacks Well With

• Thymosin Alpha-1 – broad immune modulation and tissue repair synergy
• KPV – anti-inflammatory and gut/skin healing complement
• BPC-157 – systemic healing and neuroprotective stack
• LL-37 – innate immune support complement

Use Cases

• Neuropathic Pain (diabetic neuropathy, sarcoidosis-related neuropathy)
• Small Fiber Neuropathy — Phase II data supports nerve regeneration
• Neuroprotection
• Anti-Inflammatory (chronic inflammation, autoimmune conditions)
• Sarcoidosis management
• Tissue Protection (cardiac, renal, neural cytoprotection)
• Immune Modulation

Contraindications & Safety

• WADA prohibited — classified as EPO mimetic (S2); athletes must not use
• Thrombotic risk — much lower than EPO but theoretical IRR-mediated effects; monitor in high-risk patients
• Pregnancy — insufficient data
• Generally well-tolerated in Phase II trials; favorable safety profile vs. EPO
• Common side effects: Mild injection site reaction; no significant hematological effects

Storage

• Lyophilized: -20°C long-term; 2–8°C for weeks
• Reconstituted: 2–8°C for 1–2 weeks; protect from light
• Solvent: Bacteriostatic water or sterile saline

PubMed Research

Research links will be added after PubMed search

Sources

• The Peptides Bible – Immune and neuroprotective peptides
• Peptide Protocols Master Bible – Neuropathy protocols
• Brines et al. — IRR and ARA-290 foundational research; MOLI-SATT trial data

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