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Neurological — NeuroprotectiveResearch Use

ARA-290

Also known as: Cibinetide · Innate Repair Receptor agonist

MW

1257.35 Da

Amino Acids

11 AA

Half-Life

12-14 hours

Route

SubQ

Formula

C52H90N16O21

Amino Acid Sequence

QEQLERALNSS

Mechanism of Action

ARA-290 (Cibinetide) is an 11-amino acid peptide derived from the B helix of erythropoietin (EPO). It binds the innate repair receptor (IRR), a heterodimer of EPOR (EPO receptor) and βcR (beta common receptor), NOT the classical erythropoietic EPO receptor homodimer.

PRIMARY MECHANISM — IRR ACTIVATION: The IRR is expressed on immune cells, endothelial cells, Schwann cells, and neurons. Activation triggers anti-inflammatory and tissue-protective signaling cascades including JAK2/STAT3 and PI3K/AKT pathways — WITHOUT stimulating red blood cell production (no erythropoietic effects).

ANTI-INFLAMMATORY: NF-κB suppression → reduced TNF-α, IL-1β, IL-6 in inflamed tissue. Promotes M2 macrophage polarization (tissue repair phenotype).

SMALL FIBER NEUROPATHY REPAIR: ARA-290's most studied clinical application. Promotes Schwann cell survival and axonal regeneration in damaged small nerve fibers. Phase II trials showed improvement in small fiber neuropathy symptoms and corneal nerve fiber density.

The separation of tissue-protective from erythropoietic EPO effects was a key pharmacological innovation — EPO itself cannot be used for neuroprotection because it causes dangerous polycythemia (excess red blood cells).

Dosing Protocol

Low Dose

███ – ███ mcg/day

Standard Dose

███ mcg/day

High Dose

███ – ███ mcg/day

Dosing protocols are for paid members

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Frequency

3x/week (SubQ or IV).

Half-Life

12-14 hours

Reconstitution Guide

Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.

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Clinical Warnings

Research phase only — not FDA approved.

Limited long-term safety data.

Does not affect red blood cell production (unlike EPO).

Manufacturing limited to research settings.

Contraindications

Absolute

Pregnancy

Relative Cautions

Hematologic malignancies

Polycythemia

Side Effect Profile

Mild

  • Injection site reaction
  • Mild headache

Moderate

  • Dizziness
  • Fatigue
  • Nausea

Synergistic Peptides

BPC-157NAD+SS-31

Common Stacks

BPC-157

NAD+

Research Status

PHASE II DATA. PMID 23563706 (Heij 2012): Sarcoidosis SFN RCT, pain reduction, SFNSL improvement. PMID 25402832 (Brines 2014): T2D neuropathy, 4 mg SubQ x28 days, HbA1c + neuropathic symptoms improved. PMID 27913395 (Culver 2017): Corneal nerve fiber increase confirmed.

Frequently Asked Questions

How does ARA-290 work?

ARA-290 (Cibinetide) is an 11-amino acid peptide derived from the B helix of erythropoietin (EPO). It binds the innate repair receptor (IRR), a heterodimer of EPOR (EPO receptor) and βcR (beta common receptor), NOT the classical erythropoietic EPO receptor homodimer. PRIMARY MECHANISM — IRR ACTIVATION: The IRR is expressed on immune cells, endothelial cells, Schwann cells, and neurons. Activation triggers anti-inflammatory and tissue-protective signaling cascades including JAK2/STAT3 and PI3K/A

What is the standard dose of ARA-290?

ARA-290 dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: 3x/week (SubQ or IV).

What is the half-life of ARA-290?

The half-life of ARA-290 is 12-14 hours. This determines optimal dosing frequency and timing.

Who should not use ARA-290?

ARA-290 is absolutely contraindicated in: Pregnancy. Use with caution in: Hematologic malignancies; Polycythemia.

What are the side effects of ARA-290?

Common mild side effects include: Injection site reaction, Mild headache. Moderate effects: Dizziness, Fatigue, Nausea.

What peptides stack well with ARA-290?

ARA-290 is commonly stacked with: BPC-157, NAD+, SS-31.

How do you reconstitute ARA-290?

ARA-290 is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.

How long should you cycle ARA-290?

ARA-290 cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.

References & Citations

2 PubMed studies · 3 clinical trials

The time to develop treatments for diabetic neuropathy.

Rendell Marc S. Expert opinion on investigational drugs. 2021

PubMed: 33423557DOI ↗C — Research Article

Diabetic neuropathy is a multifaceted condition affecting up to 50% of individuals with long standing diabetes. The most common presentation is peripheral diabetic sensory neuropathy (DPN). We carried

Corneal nerve fiber size adds utility to the diagnosis and assessment of therapeutic response in patients with small fiber neuropathy.

Brines Michael, Culver Daniel A, Ferdousi Maryam, Tannemaat Martijn R et al.. Scientific reports. 2018

PubMed: 29549285DOI ↗C — Research Article

Small fiber neuropathy (SFN) is a common feature of many inflammatory diseases, often presenting with pain and disability. SFN is diagnosed using symptoms, thermal threshold testing, and intra-epiderm

Registered Clinical Trials

ARA290 in T2D (Effects of ARA 290, an Erythropoietin Analogue) in Prediabetes and Type 2 Diabetes)

NCT01933529UNKNOWNPHASE2

The Use of ARA290 for the Treatment of Diabetic Macular Oedema

NCT06626971TERMINATEDPHASE2

Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis

NCT02039687COMPLETEDPHASE2

Symptom Indications

NeuropathyDiabetic neuropathySarcoidosisChronic painNerve injury

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This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.