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phase 2Pain & Recovery

ARA-290

Also known as: Cibinetide, ARA 290, Helix B Surface Peptide, EPO-derived Peptide

ARA-290 (cibinetide) is a synthetic 11-amino acid peptide derived from the B-helix surface of erythropoietin (EPO). Unlike EPO itself, ARA-290 selectively activates the innate repair receptor (IRR), a heterodimer of the EPO receptor and the beta common receptor (CD131), without stimulating erythropoiesis. This gives it potent tissue-protective and anti-inflammatory properties without the blood-thickening risks of EPO. It has completed phase 2 trials for painful neuropathy in sarcoidosis and type 2 diabetes.

3 cited references·5 researched benefits

Quick Answer

ARA-290 (cibinetide) is an 11-amino acid peptide derived from erythropoietin that selectively activates the innate repair receptor without stimulating red blood cell production. It has completed phase 2 clinical trials for neuropathic pain in sarcoidosis and diabetic neuropathy, demonstrating significant improvements in small nerve fiber density and pain reduction. ARA-290 represents a novel approach to tissue repair and neuroprotection distinct from traditional pain management.

Key Facts

Mechanism
ARA-290 selectively binds the innate repair receptor (IRR), a heterodimer composed of the erythropoietin receptor (EPOR) and the beta common receptor (βcR/CD131). This receptor is expressed on tissue-protective cells including neurons, endothelial cells, and immune cells but is distinct from the classical EPOR homodimer that drives erythropoiesis. Activation of the IRR triggers anti-apoptotic pathways (JAK2/STAT5, PI3K/Akt), suppresses NF-κB–mediated inflammation, promotes Schwann cell survival and axonal regeneration, and facilitates small nerve fiber repair. Because ARA-290 does not activate the erythropoietic EPOR homodimer, it produces no increase in red blood cell production or thrombotic risk.
Research Status
phase 2
Half-Life
~2 minutes (rapidly cleared but initiates sustained tissue-repair signaling)
Molecular Formula
C₅₅H₉₂N₁₆O₁₈
Primary Use
Pain & Recovery
Table of Contents

Benefits

  • Significant improvement in small nerve fiber density in sarcoidosis-associated neuropathy after 28 days of treatmentmoderate
  • Reduction in neuropathic pain scores in patients with painful diabetic neuropathymoderate
  • Tissue-protective and anti-inflammatory effects without erythropoietic stimulation or thrombotic riskstrong
  • Promotes corneal nerve fiber regeneration in patients with small fiber neuropathymoderate
  • Potential cardioprotective effects through anti-apoptotic signaling in ischemic tissuepreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection4 mgOnce dailyPhase 2 trial dosing for sarcoidosis neuropathy. 28-day treatment cycles showed significant improvement in nerve fiber density.
Intravenous infusion2–8 mgSingle dose or short courseEarly clinical studies used IV dosing for acute tissue protection models. Subcutaneous dosing is preferred for chronic neuropathy.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Injection site reactions (mild redness or discomfort)common
  • Transient headache reported in some trial participantscommon
  • Mild gastrointestinal discomfort (nausea)rare
  • No serious adverse events related to treatment observed in phase 2 trialsrare

Frequently Asked Questions

How is ARA-290 different from EPO (erythropoietin)?
ARA-290 is derived from a small region of the EPO molecule but acts on a completely different receptor. EPO activates the classical EPOR homodimer to stimulate red blood cell production, which carries risks of blood thickening and thrombosis. ARA-290 selectively activates the innate repair receptor (IRR), a heterodimer of EPOR and CD131, which triggers tissue protection and repair without any effect on red blood cell production. This makes ARA-290 safe from the cardiovascular risks associated with EPO.
What conditions has ARA-290 been tested for in clinical trials?
ARA-290 has completed phase 2 clinical trials for sarcoidosis-associated small fiber neuropathy, where it demonstrated significant improvements in corneal and skin nerve fiber density and reductions in pain scores. It has also been studied in type 2 diabetes-related neuropathy and shows promise for other conditions involving small nerve fiber damage, chronic pain, and tissue injury. Research into its cardioprotective and anti-inflammatory applications continues.
Why does ARA-290 have such a short half-life but prolonged effects?
Although ARA-290 is cleared from the bloodstream within minutes, its binding to the innate repair receptor initiates intracellular signaling cascades (JAK2/STAT5, PI3K/Akt) that persist long after the peptide itself is gone. These pathways activate gene transcription programs for anti-apoptotic and regenerative processes that unfold over days to weeks. This is why daily dosing in clinical trials produced cumulative nerve fiber regeneration measured over 28 days.

References

  1. 1
    ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes(2012)PubMed ↗
  2. 2
    Cibinetide (ARA 290) improves small nerve fiber density and pain in sarcoidosis patients: a randomized controlled trial(2014)PubMed ↗
  3. 3
    The innate repair receptor: a novel concept for tissue protection and repair mediated by the EPO receptor/CD131 heterodimer(2010)PubMed ↗

Latest Research

Last updated: 2026-02-19