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Library/For Cognition/ARA-290 (Cibinetide)
RUO · Phase 2EPO-Derived+2 more

ARA-290 (Cibinetide)

An 11-amino-acid peptide derived from the helix B region of erythropoietin. We read all 58 studies. The protocol is below.

Updated 03 May 2026Read 12 minEvidence ●●●○○Citations 58
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The ARA-290 (Cibinetide) Report · $19

Everything you need to start: dose, sourcing, safety, our verdict.

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Built from 58 cited studies.

Status
Research-only
Class
EPO-Derived
Evidence
3/ 5●●●○○
FDA status
$19 ↓
Phase 2 indications studied
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Studied population
$19 ↓
Read this if
  • **you have a documented small-fiber-neuropathy diagnosis** (skin biopsy + IENFD count) — you're the trial population
  • you have sarcoidosis-associated small fiber neuropathy and your rheumatologist mentioned it
  • you've been told you have painful diabetic neuropathy and gabapentin didn't work
  • you're long-COVID and tracking the EPO-derived anti-inflammatory literature
Skip this if
  • you don't have a confirmed small-fiber-neuropathy diagnosis — the trial signal does not generalize to "I feel inflamed"
  • you want a phase 3 trial — there isn't one
  • you're shopping for general "anti-inflammatory" without a specific neuropathy diagnosis
  • you have active malignancy or are pregnant — the long-term safety is unmapped
  • your post-dose blood work shows a hemoglobin or hematocrit spike — **real ARA-290 does NOT raise Hgb**. A spike means the vial is likely counterfeit EPO — different molecule, different risk profile (thrombosis, hypertension, stroke). Stop, retest, do not redose.
The 4 ways you can buy ARA-290 (Cibinetide)
Brand
✗
No FDA approval
Compounded 503A
✓
Rare; investigational comp…
$200–$400/mo where available
Hard to source legally pre-approval; very few compounders engage.
RUO (research-only)
✓
Sold for research only
$120–$250/mo
Dominant off-label channel; identity and purity unverified.
Gray market
✓
Illegal to import for huma…
$85–$95/mo
Niche neuropathy use; small but live gray-channel.
Click any lane for the full Sourcing breakdown.
First 90 days · ARA-290 (Cibinetide)
Weeks 1–2
Defined-course peptide, not a chronic stack. The Heij/Dahan small-fiber neuropathy trials ran ~28 days subQ — that's your protocol shape. Track pain scores (NRS 0-10) AND IENFD biopsy if you have access; without before/after pain data this is a placebo experiment.
Weeks 4–8
28-day course endpoint. If pain scores haven't dropped by ≥30% by end of week 4, the trial-grade signal isn't appearing for you — that's a real response rate ceiling, not a 'titrate longer' problem.
Week 12 — decide
ARA-290 was not designed for chronic use. By week 12 you should either be off it (course complete) OR have a documented partial response that justifies a single second course, NOT a continuous prescription. Chronic dosing has no published safety data.
Quit if
  • End of 28 days with no measurable pain-score change — non-responder. Don't extend the course hoping for a delayed response.
  • You don't have biopsy-confirmed small-fiber neuropathy — the trial population is documented SFN, not generalized neuropathy or fibromyalgia.
  • Cardiac or hematologic symptoms — the parent molecule (EPO) drives RBC production; ARA-290 was designed to avoid that, but the safety data is small.
  • Tempted to stack with other erythropoietic agents (EPO, darbepoetin) — opposite-direction safety signal; do not co-administer.
Identity

What it is.

ARA-290 (cibinetide) is an 11-amino-acid derived from the B-helix of erythropoietin (EPO). It was designed by Anthony Cerami's group specifically to capture EPO's tissue-protective and anti-inflammatory effects without raising red blood cell count.

The biology behind that split is real. EPO has two distinct receptor systems: the classical EPO-R homodimer (which raises hematocrit and is the basis for EPO as a drug and as a doping agent) and a separate innate repair receptor (EPO-R/βcR heterodimer) involved in tissue protection, neuroprotection, and resolving inflammation. ARA-290 binds the second system without engaging the first.

It was developed by Araim Pharmaceuticals and taken into Phase 2 trials for sarcoidosis-associated small-fiber neuropathy and diabetic neuropathy. It is not FDA-approved. Sold as . Notably, it does not raise hematocrit and is not on the WADA prohibited list.

TL;DR

TL;DR. 30-second version.

The compressed verdict — what ARA-290 (Cibinetide) actually is, what the human evidence shows, and the watch-for in three bullets. Locked.

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Mechanism

Mechanism.

Mechanism · in the ARA-290 (Cibinetide) report

How the molecule actually works — receptor profile, downstream signaling, what to expect mechanistically.

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Evidence

Evidence. What we actually know in humans.

Evidence · in the ARA-290 (Cibinetide) report

The trial breakdown — phase, n, primary endpoint, who funded, what hit, what didn't.

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Human-Evidence Factbox
FDA status
$19 ↓
Phase 2 indications studied
$19 ↓
Studied population
$19 ↓
"General anti-inflammatory" data
$19 ↓
Erythropoietic effect
$19 ↓
Mechanism
$19 ↓
Phase 3 completed
$19 ↓
Major adverse events flagged
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Hgb/hematocrit on real ARA-290
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Dose

Dose. The actual protocol.

Dose · in the ARA-290 (Cibinetide) report

The specific protocol — dose, titration schedule, cycle pattern, frequency, route.

We read 58 studies to write this report.
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Sourcing

Sourcing. Where the cohort actually buys.

Sourcing · in the ARA-290 (Cibinetide) report

Sourcing breakdown — vendor methodology, red flags, our published test results, COA checklist.

We read 58 studies to write this report.
Get the report · $19 ↓
Safety

Safety. Side effects.

Safety · in the ARA-290 (Cibinetide) report

The watch-for list — contraindications, drug interactions, monitoring labs, when to stop.

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Editorial Position

Editorial position.

Editorial Position · in the ARA-290 (Cibinetide) report

Our editorial position — explicit yes / no / depends, with the reasoning behind it.

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Citations

Citations.

  1. 01Tracey KJ. Editorial. Molecular medicine (Cambridge, Mass.). 2013;19(1):333. PMID: 24178588.
  2. 02van Velzen M, et al. ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert opinion on investigational drugs. 2014;23(4):541-50. PMID: 24555851.
  3. 03Zhang W, et al. ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides. 2016;76:73-9. PMID: 26774587.
  4. 04Rendell MS. The time to develop treatments for diabetic neuropathy. Expert opinion on investigational drugs. 2021;30(2):119-130. PMID: 33423557.
  5. 05Al-Onaizi MA, et al. Early monocyte modulation by the non-erythropoietic peptide ARA 290 decelerates AD-like pathology progression. Brain, behavior, and immunity. 2022;99:363-382. PMID: 34343617.
+Show all 58 citations
  1. 06Nairz M, et al. Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis. Scientific reports. 2017;7(1):13012. PMID: 29026145.
  2. 07Watanabe M, et al. A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets. Transplantation. 2016;100(3):554-62. PMID: 26683514.
  3. 08Brines M, et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Molecular medicine (Cambridge, Mass.). 2015;20(1):658-66. PMID: 25387363.
  4. 09Yao M, et al. Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation. Cell transplantation. 2021;30:9636897211039739. PMID: 34498509.
  5. 10Yao M, et al. Improvement of Islet Allograft Function Using Cibinetide, an Innate Repair Receptor Ligand. Transplantation. 2020;104(10):2048-2058. PMID: 32345869.
  6. 11Mohtavinejad N, et al. Synthesis and evaluation of (99m)Tc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region. Iranian journal of basic medical sciences. 2021;24(11):1488-1499. PMID: 35317117.
  7. 12Lois N, et al. A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema. Journal of clinical medicine. 2020;9(7). PMID: 32674280.
  8. 13Heij L, et al. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Molecular medicine (Cambridge, Mass.). 2012;18(1):1430-6. PMID: 23168581.
  9. 14Bitto A, et al. Activation of the EPOR-β common receptor complex by cibinetide ameliorates impaired wound healing in mice with genetic diabetes. Biochimica et biophysica acta. Molecular basis of disease. 2018;1864(2):632-639. PMID: 29223734.
  10. 15Swartjes M, et al. 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. Molecular pain. 2014;10:13. PMID: 24529189.
  11. 16Brines M, et al. Corneal nerve fiber size adds utility to the diagnosis and assessment of therapeutic response in patients with small fiber neuropathy. Scientific reports. 2018;8(1):4734. PMID: 29549285.
  12. 17Culver DA, et al. Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain. Investigative ophthalmology & visual science. 2017;58(6):BIO52-BIO60. PMID: 28475703.
  13. 18Dahan A, et al. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Molecular medicine (Cambridge, Mass.). 2013;19(1):334-45. PMID: 24136731.
  14. 19Sun Y, et al. Phase-targeted erythropoietin derivatives for traumatic brain injury: bridging mechanisms to precision therapy. Frontiers in neurology. 2026;16:1665405. PMID: 41659975.
  15. 20Winicki NM, et al. A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan. Frontiers in cardiovascular medicine. 2023;9:1096887. PMID: 36741836.
  16. 21Atkins C, et al. Managing fatigue in sarcoidosis - A systematic review of the evidence. Chronic respiratory disease. 2017;14(2):161-173. PMID: 27507833.
  17. 22Awida Z, et al. The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice. International journal of molecular sciences. 2021;23(1). PMID: 35008482.
  18. 23Liu Y, et al. Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection. PloS one. 2014;9(3):e90942. PMID: 24603865.
  19. 24O'Leary OE, et al. The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic. Experimental eye research. 2019;182:144-155. PMID: 30876881.
  20. 25Liu G, et al. The protective effect of erythropoietin and its novel derived peptides in peripheral nerve injury. International immunopharmacology. 2024;138:112452. PMID: 38943972.
  21. 26Joshi D, et al. Potential role of erythropoietin receptors and ligands in attenuating apoptosis and inflammation in critical limb ischemia. Journal of vascular surgery. 2014;60(1):191-201, 201.e1-2. PMID: 24055514.
  22. 27Collino M, et al. Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin. Pharmacology & therapeutics. 2015;151:32-40. PMID: 25728128.
  23. 28van Rijt WG, et al. Erythropoietin-mediated protection in kidney transplantation: nonerythropoietic EPO derivatives improve function without increasing risk of cardiovascular events. Transplant international : official journal of the European Society for Organ Transplantation. 2014;27(3):241-8. PMID: 23964738.
  24. 29Heij L, et al. Sarcoidosis and pain caused by small-fiber neuropathy. Pain research and treatment. 2012;2012:256024. PMID: 23304492.
  25. 30Wang RL, et al. Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke. CNS neuroscience & therapeutics. 2024;30(3):e14676. PMID: 38488446.
  26. 31Huang B, et al. Non-erythropoietic erythropoietin-derived peptide protects mice from systemic lupus erythematosus. Journal of cellular and molecular medicine. 2018;22(7):3330-3339. PMID: 29570934.
  27. 32Alasousi D, et al. Immunometabolic dysregulation drives selective executive cognitive dysfunction in male db/db mice. Neurobiology of disease. 2026;223:107376. PMID: 41933665.
  28. 33Ghassemi-Barghi N, et al. Mechanistic Approach for Protective Effect of ARA290, a Specific Ligand for the Erythropoietin/CD131 Heteroreceptor, against Cisplatin-Induced Nephrotoxicity, the Involvement of Apoptosis and Inflammation Pathways. Inflammation. 2023;46(1):342-358. PMID: 36085231.
  29. 34Swartjes M, et al. Ketamine does not produce relief of neuropathic pain in mice lacking the β-common receptor (CD131). PloS one. 2013;8(8):e71326. PMID: 23936499.
  30. 35Shokrzadeh M, et al. An engineered non-erythropoietic erythropoietin-derived peptide, ARA290, attenuates doxorubicin induced genotoxicity and oxidative stress. Toxicology in vitro : an international journal published in association with BIBRA. 2020;66:104864. PMID: 32335150.
  31. 36Gammella E, et al. Erythropoietin's inhibiting impact on hepcidin expression occurs indirectly. American journal of physiology. Regulatory, integrative and comparative physiology. 2015;308(4):R330-5. PMID: 25519735.
  32. 37Thevis M, et al. Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions. Expert review of proteomics. 2014;11(6):663-73. PMID: 25382550.
  33. 38Thomas A, et al. Characterization of in vitro generated metabolites of selected peptides <2 kDa prohibited in sports. Drug testing and analysis. 2017;9(11-12):1799-1803. PMID: 28941172.
  34. 39Dennhardt S, et al. Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice. Frontiers in immunology. 2022;13:1010882. PMID: 36211426.
  35. 40Xie J, et al. Mesoporous Silica Particles as a Multifunctional Delivery System for Pain Relief in Experimental Neuropathy. Advanced healthcare materials. 2016;5(10):1213-21. PMID: 27028159.
  36. 41Zhao LJ, et al. ARA290 inhibits high glucose-induced apoptosis of NRK-52E cells. Journal of biological regulators and homeostatic agents. 2021;35(3):1169-1176. PMID: 34134477.
  37. 42Thomas A, et al. Simplifying and expanding the screening for peptides <2 kDa by direct urine injection, liquid chromatography, and ion mobility mass spectrometry. Journal of separation science. 2016;39(2):333-41. PMID: 26578461.
  38. 43Chen H, et al. Therapeutic effects of nonerythropoietic erythropoietin analog ARA290 in experimental autoimmune encephalomyelitis rat. Journal of neuroimmunology. 2014;268(1-2):64-70. PMID: 24518674.
  39. 44Sanchis-Gomar F, et al. Erythropoietin receptor (EpoR) agonism is used to treat a wide range of disease. Molecular medicine (Cambridge, Mass.). 2013;19(1):62-4. PMID: 23615965.
  40. 45Robertson CS, et al. Treatment of mild traumatic brain injury with an erythropoietin-mimetic peptide. Journal of neurotrauma. 2013;30(9):765-74. PMID: 22827443.
  41. 46Korokin M, et al. Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia. International journal of molecular sciences. 2020;21(18). PMID: 32942669.
  42. 47Merzbach S, et al. Anti-Inflammatory Effects of Clarstatin, a Shared-Epitope-Antagonistic Cyclic Peptide, on Experimental Autoimmune Uveitis in Mice. Investigative ophthalmology & visual science. 2025;66(1):13. PMID: 39775697.
  43. 48van Rijt WG, et al. Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury. Journal of translational medicine. 2013;11:286. PMID: 24225194.
  44. 49Dooley K, et al. Functionalized Biopolymer Particles Enhance Performance of a Tissue-Protective Peptide under Proteolytic and Thermal Stress. Biomacromolecules. 2016;17(6):2073-9. PMID: 27219509.
  45. 50Cerit H, et al. Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2015;25(12):2289-99. PMID: 26431906.
  46. 51Yan L, et al. EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway. Transplantation proceedings. 2018;50(5):1575-1582. PMID: 29880388.
  47. 52Swartjes M, et al. Assessment of allodynia relief by tissue-protective molecules in a rat model of nerve injury-induced neuropathic pain. Methods in molecular biology (Clifton, N.J.). 2013;982:187-95. PMID: 23456870.
  48. 53Dilley A. ARA290 in a rat model of inflammatory pain. Methods in molecular biology (Clifton, N.J.). 2013;982:213-25. PMID: 23456872.
  49. 54Hache G, et al. ARA290, a Specific Agonist of Erythropoietin/CD131 Heteroreceptor, Improves Circulating Endothelial Progenitors' Angiogenic Potential and Homing Ability. Shock (Augusta, Ga.). 2016;46(4):390-7. PMID: 27172159.
  50. 55Devalliere J, et al. Co-delivery of a growth factor and a tissue-protective molecule using elastin biopolymers accelerates wound healing in diabetic mice. Biomaterials. 2017;141:149-160. PMID: 28688286.
  51. 56van Rijt WG, et al. ARA290, a non-erythropoietic EPO derivative, attenuates renal ischemia/reperfusion injury. Journal of translational medicine. 2013;11:9. PMID: 23302512.
  52. 57Pulman KG, et al. The erythropoietin-derived peptide ARA290 reverses mechanical allodynia in the neuritis model. Neuroscience. 2013;233:174-83. PMID: 23262243.
  53. 58Kawakami M. Discovery of tumor necrosis factor (TNF) and identification of the potential of anti-TNF antibodies in Dr. Cerami's laboratory. Molecular medicine (Cambridge, Mass.). 2014;20 Suppl 1(Suppl 1):S17-9. PMID: 25549227.
The ARA-290 (Cibinetide) Report · $19

Everything you need to start.

Dose, sourcing, safety, our verdict. One purchase. Yours forever.

Built from 58 cited studies.

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