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ARA-290

ARA-290 is a synthetic 11-amino acid peptide derived from the tissue-protective domain of erythropoietin (EPO), specifically engineered to retain neuroprotective and tissue-protective properties while eliminating erythropoietic activity. This investigational peptide activates the innate repair receptor (IRR) also known as the common β-receptor (CD131), which plays a crucial role in tissue protection, repair, and regeneration processes.

Unlike native erythropoietin, ARA-290 does not stimulate red blood cell production, making it of research interest without the cardiovascular risks associated with increased hematocrit. The peptide has been studied in diabetic neuropathy, chronic neuropathic pain, and inflammatory conditions. Phase II results were mixed: symptom improvement was reported in type 2 diabetic neuropathy, while controlled pain outcomes in sarcoidosis did not separate from placebo.

Black and white logo with abstract circular design and the word 'Cibinetide'.

Overview

ARA-290 was specifically designed through peptide engineering to isolate the tissue-protective properties of erythropoietin from its hematopoietic effects. The peptide maintains the critical binding domain necessary for IRR activation while eliminating sequences responsible for erythropoiesis. The peptide demonstrates high bioavailability (>85%) via subcutaneous injection and is metabolized primarily in the liver with renal elimination.

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Chemical structure & Properties

  • Molecular Formula: C51H84N16O21
  • Molecular Weight: ~1,257.3 Da
  • Sequence: Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser, with a pyroglutamate cap on the N-terminus
  • Half-life: Approximately 2 minutes in plasma; the tissue-protective effects outlast the exposure
  • Stability: Stable in lyophilized form, requires refrigeration when reconstituted

Mechanism of Action

ARA-290 exerts its therapeutic effects through multiple interconnected molecular pathways:

Innate Repair Receptor (IRR) Activation

ARA-290's primary mechanism involves selective binding to the IRR complex:

  • Selective binding to CD131 (common β-receptor) and EPO receptor
  • Activation of tissue-protective signaling without erythropoietic stimulation
  • Initiation of cellular repair and survival pathways
  • Enhanced tissue resilience against oxidative and inflammatory damage

Neuroprotection and Neural Repair

The peptide demonstrates significant neuroprotective properties through:

  • Prevention of neuronal apoptosis and oxidative damage
  • Enhancement of nerve growth factor expression and signaling
  • Promotion of axonal regeneration and remyelination processes
  • Improvement of neuronal survival under stress conditions

Anti-inflammatory Effects

ARA-290 exhibits potent anti-inflammatory properties through:

  • Suppression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6)
  • Reduction of nuclear factor-kappa B (NF-κB) activation
  • Enhancement of anti-inflammatory mediator expression
  • Modulation of microglial activation and neuroinflammation

Vascular Protection and Repair

The peptide promotes vascular health through:

  • Improvement of endothelial function and nitric oxide bioavailability
  • Enhancement of microvascular circulation, particularly in peripheral tissues
  • Protection against ischemia-reperfusion injury
  • Promotion of angiogenesis and vascular repair processes

Areas Investigated in

the Research Literature

Neurological Applications

Diabetic Neuropathy: Clinical studies demonstrate ARA-290's efficacy in treating:

  • Peripheral diabetic neuropathy with significant pain reduction
  • Improvement in nerve conduction velocities and sensory function
  • Enhanced quality of life measures and functional capacity
  • Reduction in diabetes-related complications

Mechanism: ARA-290 protects against hyperglycemia-induced neural damage, promotes nerve regeneration, and improves microvascular circulation to peripheral nerves.

Chronic Neuropathic Pain: Research indicates potential benefits in:

  • Sarcoidosis-associated neuropathy — investigated; controlled pain outcomes did not separate from placebo
  • Post-herpetic neuralgia and viral-induced neuropathy
  • Chemotherapy-induced peripheral neuropathy
  • Complex regional pain syndrome

Inflammatory Applications

Anti-inflammatory Effects: ARA-290 demonstrates protective effects against:

  • Chronic inflammatory neuropathies
  • Autoimmune inflammatory responses
  • Tissue damage in chronic inflammatory states
  • Inflammatory pain syndromes

Mechanism: Modulation of inflammatory cascades, reduction of cytokine production, and enhancement of tissue repair processes.

Vascular Applications

Microcirculation Enhancement: Preclinical evidence supports potential benefits in:

  • Peripheral vascular disease
  • Lower extremity vascular insufficiency
  • Wound healing enhancement in diabetic ulcers
  • Prevention of ischemia-reperfusion injury

Mechanism: Improved endothelial function, enhanced microvascular circulation, and promotion of adaptive tissue protection.

Patient consulting with Dr. Ched Garten at Paragon, symbolizing advanced non-surgical care for joint, tendon, muscle, and pain issues.

Current Clinical Evidence

Safety Profile and Considerations

Clinical Safety Data

Common Adverse Events (Rare):

  • Injection site reactions: mild pain, redness, or swelling (<5% incidence)
  • Gastrointestinal effects: occasional nausea (<3% incidence)
  • Headaches: mild headaches in some patients (<2% incidence)
  • Fatigue: transient during treatment initiation (<2% incidence)

Potential Concerns

Theoretical Risks:

  • No evidence of erythropoietic effects or increased cardiovascular risk
  • Minimal drug interaction potential identified
  • No immunogenic responses or antibody formation observed
  • Excellent tolerability across clinical studies

Drug Interactions:

  • Limited data on interactions with other medications
  • Consultation with healthcare providers recommended for complex cases

Contraindications

ARA-290 should be avoided in:

  • Known hypersensitivity to ARA-290 or formulation components
  • Active malignancy (theoretical concern regarding tissue-protective effects)
  • Pregnancy and breastfeeding (insufficient safety data)
  • Severe cardiovascular disease without medical supervision

Regulatory Status and Legal Considerations

Regulatory information current as of 28 August 2026. This is a summary, not legal or medical advice, and status can change.

FDA Status

  • Classification: Investigational drug under clinical development
  • Approval Status: Not approved for commercial therapeutic use
  • Research Status: Available for clinical trials and expanded access programs
  • Regulatory Position: Phase II completed, Phase III studies needed for approval

International Status

  • EMA: Orphan drug designation potential for rare neuropathic conditions
  • Other Regions: Early-stage regulatory interactions initiated
  • Clinical Access: Limited to research protocols and compassionate use cases

Legal Availability

  • Commercial Status: Not legally available as prescription medication
  • Market Presence: Limited to clinical trial participants
  • Quality Control: Clinical-grade material produced under GMP conditions
  • Clinical Use: Restricted to research settings and experimental protocols
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Conclusion

What the evidence supports

ARA-290 is an investigational peptide that activates the innate repair receptor and has been studied in Phase II human trials of diabetic neuropathy and chronic neuropathic pain. Results were mixed: symptom improvement was reported in type 2 diabetic neuropathy, while controlled pain outcomes in sarcoidosis did not separate from placebo. It has not completed Phase III trials, and there is no established dosing or long-term safety profile. ARA-290 is not FDA approved and is limited to research protocols and compassionate-use access. This page summarizes the published research and nothing further.

ARA-290 SCIENTIFIC

DATA SUMMARY

MOLECULAR CHARACTERISTICS
PRECLINICAL EFFICACY DATA
CLINICAL EVIDENCE SUMMARY
SAFETY PROFILE
REGULATORY STATUS
Parameter
Molecular Weight
Amino Acid Length
Half-Life
Bioavailability
Detection Window
Value
approx. 1,257.3 Da
11 residues
6-8 hours (hepatic)
High via subcutaneous (>85%)
Not established
Application
Diabetic Neuropathy
Neuropathic Pain
Neural Protection
Anti-inflammatory
Reported outcome (model)
Significant pain reduction, improved nerve function
Did not separate from placebo
Enhanced axonal regeneration
Reduced cytokines, tissue protection
Study Type
Phase II Trial
Sarcoidosis Study
Safety Studies
Population
Diabetic neuropathy patients
Chronic pain patients
Various populations
Results
Positive efficacy results
Did not separate from placebo on controlled endpoints
Excellent tolerability
Limitations
Phase III studies needed
Limited sample size
Long-term data needed
Parameter
Acute Toxicity
Organ Toxicity
Adverse Events
Long-term Safety
Finding
No dose-limiting toxicity in preclinical toxicology; no established human therapeutic dose exists
No hematocrit changes or cardiovascular effects
Minimal reported in clinical studies
No long-term human safety data; follow-up limited to the completed Phase II trials
Authority
FDA
WADA Status
DEA
Classification
Investigational Drug
S0 Non-approved Substance
Unscheduled
Status
Phase II completed, Phase III needed
Prohibited at all times under S0
Not controlled substance

About this library

This library is published for education. It summarizes published research on compounds studied in this field. Many have no approved medical use, and several cannot lawfully be compounded in the United States. The presence of a page here does not mean Paragon offers that compound. Nothing on these pages is an offer to treat.

This page is general education about a compound studied in this field. Nothing here is medical advice, a recommendation, or an offer to prescribe or supply. A page appearing in this library does not mean Paragon Sports Medicine offers that compound.

Disclaimer: This information is provided for educational purposes only and does not constitute medical advice. ARA-290 is currently investigational and not approved by the FDA for routine therapeutic use. Access is limited to clinical trials and expanded access programs. Patients should consult with qualified healthcare providers before considering any experimental peptide therapy.

Statements on this page have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease. Many peptides described here are not FDA approved for the uses discussed, and some cannot lawfully be compounded in the United States. Nothing on this page is medical advice or a recommendation for any individual. Whether any therapy is appropriate depends on your history, your laboratory results, and a clinical evaluation. Individual results vary. This page is published for education. Use of this site does not create a physician-patient relationship.

References

01
ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Mol Med. 2015.
02
ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opin Investig Drugs. 2014.
03
ARA 290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain coupled with suppression of the spinal microglia response. Mol Pain. 2014.
04
ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides. 2016.
05
A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema. J Clin Med. 2020.