ARA-290

Key Benefits#

• Reduces neuropathic pain from small fiber neuropathy
• Anti-inflammatory without immune suppression
• Tissue protection after ischemia/reperfusion injury
• Promotes nerve fiber regeneration
• Improves symptoms of sarcoidosis-associated neuropathy
• May reduce insulin resistance and improve metabolic health
• Shown to improve autonomic neuropathy symptoms

Mechanism of Action#

ARA-290 selectively binds the innate repair receptor (IRR), a heterodimer of the EPO receptor and the β-common receptor (βcR). This receptor is expressed in injured tissues, macrophages, and neurons. Activation inhibits NF-κB and JAK2/STAT5 inflammatory pathways, suppresses pro-inflammatory macrophage polarization, promotes M2 (anti-inflammatory) macrophage phenotype, and stimulates nerve fiber regeneration. It does not stimulate erythropoiesis, avoiding EPO's cardiovascular side effects.

Dosing Protocols#

Side Effects#

• Injection site reactions
• Mild fatigue at initiation
• Transient warm sensation post-injection
• Rare: mild headache

Contraindications#

No known hematopoietic stimulation, making it safer than EPO. Caution in pregnancy (safety data limited). Avoid in known hypersensitivity to EPO-derived peptides.

Storage#

Store at 4°C (refrigerated), do not freeze. Stable for up to 24 months in lyophilized form. Reconstituted solution should be used within 7 days.

Featured In Stacks#

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   Phase-targeted erythropoietin derivatives for traumatic brain injury: bridging mechanisms to precision therapy

   Sun Y, Song B, Zhang Y, Zhang Y, Zhou L · Frontiers in neurology · 2025ReviewPubMed Verified

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   Anti-Inflammatory Effects of Clarstatin, a Shared-Epitope-Antagonistic Cyclic Peptide, on Experimental Autoimmune Uveitis in Mice

   Merzbach S, Schumacher-Klinger A, Klazas M, Hoffman A, Lazarovici P, Gilon C et al. · Investigative ophthalmology & visual science · 2025PubMed Verified

3. 3.
   The protective effect of erythropoietin and its novel derived peptides in peripheral nerve injury

   Liu G, Liang J, Li W, Jiang S, Song M, Xu S et al. · International immunopharmacology · 2024ReviewPubMed Verified

4. 4.
   Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke

   Wang RL, Yang ZH, Huang YY, Hu Y, Wang YL, Yan F et al. · CNS neuroscience & therapeutics · 2024PubMed Verified

5. 5.
   A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan

   Winicki NM, Nanavati AP, Morrell CH, Moen JM, Axsom JE, Krawczyk M et al. · Frontiers in cardiovascular medicine · 2022PubMed Verified

6. 6.
   Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice

   Dennhardt S, Pirschel W, Wissuwa B, Imhof D, Daniel C, Kielstein JT et al. · Frontiers in immunology · 2022PubMed Verified

7. 7.
   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

   Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, Ashari S, Ghiabi S, Bayrami Z · Inflammation · 2023PubMed Verified

8. 8.
   Synthesis and evaluation of (99m)Tc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region

   Mohtavinejad N, Hajiramezanali M, Akhlaghi M, Bitarafan-Rajabi A, Gholipour N · Iranian journal of basic medical sciences · 2021PubMed Verified

9. 9.
   The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice

   Awida Z, Bachar A, Saed H, Gorodov A, Ben-Califa N, Ibrahim M et al. · International journal of molecular sciences · 2021PubMed Verified

10. 10.
    Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation

    Yao M, Domogatskaya A, Ågren N, Watanabe M, Tokodai K, Brines M et al. · Cell transplantation · 2021PubMed Verified

11. 11.
    Early monocyte modulation by the non-erythropoietic peptide ARA 290 decelerates AD-like pathology progression

    Al-Onaizi MA, Thériault P, Lecordier S, Prefontaine P, Rivest S, ElAli A · Brain, behavior, and immunity · 2022PubMed Verified

12. 12.
    ARA290 inhibits high glucose-induced apoptosis of NRK-52E cells

    Zhao LJ, Sun XL, Qiu J, Xiao BL, Fan XY, Wang T et al. · Journal of biological regulators and homeostatic agents · 2021PubMed Verified

13. 13.
    The time to develop treatments for diabetic neuropathy

    Rendell MS · Expert opinion on investigational drugs · 2021Meta-AnalysisPubMed Verified

14. 14.
    Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

    Korokin M, Gureev V, Gudyrev O, Golubev I, Korokina L, Peresypkina A et al. · International journal of molecular sciences · 2020PubMed Verified

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    A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema

    Lois N, Gardner E, McFarland M, Armstrong D, McNally C, Lavery NJ et al. · Journal of clinical medicine · 2020PubMed Verified

16. 16.
    Improvement of Islet Allograft Function Using Cibinetide, an Innate Repair Receptor Ligand

    Yao M, Watanabe M, Sun S, Tokodai K, Cerami A, Brines M et al. · Transplantation · 2020PubMed Verified

17. 17.
    An engineered non-erythropoietic erythropoietin-derived peptide, ARA290, attenuates doxorubicin induced genotoxicity and oxidative stress

    Shokrzadeh M, Etebari M, Ghassemi-Barghi N · Toxicology in vitro : an international journal published in association with BIBRA · 2020PubMed Verified

18. 18.
    The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic

    O'Leary OE, Canning P, Reid E, Bertelli PM, McKeown S, Brines M et al. · Experimental eye research · 2019PubMed Verified

19. 19.
    EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway

    Yan L, Zhang H, Gao S, Zhu G, Zhu Q, Gu Y et al. · Transplantation proceedings · 2018PubMed Verified

20. 20.
    Non-erythropoietic erythropoietin-derived peptide protects mice from systemic lupus erythematosus

    Huang B, Jiang J, Luo B, Zhu W, Liu Y, Wang Z et al. · Journal of cellular and molecular medicine · 2018PubMed Verified

21. 21.
    Corneal nerve fiber size adds utility to the diagnosis and assessment of therapeutic response in patients with small fiber neuropathy

    Brines M, Culver DA, Ferdousi M, Tannemaat MR, van Velzen M, Dahan A et al. · Scientific reports · 2018PubMed Verified

22. 22.
    Activation of the EPOR-β common receptor complex by cibinetide ameliorates impaired wound healing in mice with genetic diabetes

    Bitto A, Irrera N, Pizzino G, Pallio G, Mannino F, Vaccaro M et al. · Biochimica et biophysica acta. Molecular basis of disease · 2018PubMed Verified

23. 23.
    Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis

    Nairz M, Haschka D, Dichtl S, Sonnweber T, Schroll A, Aßhoff M et al. · Scientific reports · 2017PubMed Verified

24. 24.
    Characterization of in vitro generated metabolites of selected peptides <2 kDa prohibited in sports

    Thomas A, Knoop A, Schänzer W, Thevis M · Drug testing and analysis · 2017PubMed Verified

25. 25.
    Co-delivery of a growth factor and a tissue-protective molecule using elastin biopolymers accelerates wound healing in diabetic mice

    Devalliere J, Dooley K, Hu Y, Kelangi SS, Uygun BE, Yarmush ML · Biomaterials · 2017PubMed Verified

26. 26.
    Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain

    Culver DA, Dahan A, Bajorunas D, Jeziorska M, van Velzen M, Aarts LPHJ et al. · Investigative ophthalmology & visual science · 2017RCTPubMed Verified

27. 27.
    Managing fatigue in sarcoidosis - A systematic review of the evidence

    Atkins C, Wilson AM · Chronic respiratory disease · 2017Meta-AnalysisPubMed Verified

28. 28.
    Functionalized Biopolymer Particles Enhance Performance of a Tissue-Protective Peptide under Proteolytic and Thermal Stress

    Dooley K, Devalliere J, Uygun BE, Yarmush ML · Biomacromolecules · 2016PubMed Verified

29. 29.
    ARA290, a Specific Agonist of Erythropoietin/CD131 Heteroreceptor, Improves Circulating Endothelial Progenitors' Angiogenic Potential and Homing Ability

    Hache G, Garrigue P, Bennis Y, Stalin J, Moyon A, Cerami A et al. · Shock (Augusta, Ga.) · 2016PubMed Verified

30. 30.
    Mesoporous Silica Particles as a Multifunctional Delivery System for Pain Relief in Experimental Neuropathy

    Xie J, Xiao D, Zhao J, Hu N, Bao Q, Jiang L et al. · Advanced healthcare materials · 2016PubMed Verified

31. 31.
    ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception

    Zhang W, Yu G, Zhang M · Peptides · 2016PubMed Verified

32. 32.
    A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets

    Watanabe M, Lundgren T, Saito Y, Cerami A, Brines M, Östenson CG et al. · Transplantation · 2016PubMed Verified

33. 33.
    Simplifying and expanding the screening for peptides <2 kDa by direct urine injection, liquid chromatography, and ion mobility mass spectrometry

    Thomas A, Görgens C, Guddat S, Thieme D, Dellanna F, Schänzer W et al. · Journal of separation science · 2016PubMed Verified

34. 34.
    Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action

    Cerit H, Veer IM, Dahan A, Niesters M, Harmer CJ, Miskowiak KW et al. · European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2015RCTPubMed Verified

35. 35.
    Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin

    Collino M, Thiemermann C, Cerami A, Brines M · Pharmacology & therapeutics · 2015ReviewPubMed Verified

36. 36.
    Discovery of tumor necrosis factor (TNF) and identification of the potential of anti-TNF antibodies in Dr. Cerami's laboratory

    Kawakami M · Molecular medicine (Cambridge, Mass.) · 2014PubMed Verified

37. 37.
    Erythropoietin's inhibiting impact on hepcidin expression occurs indirectly

    Gammella E, Diaz V, Recalcati S, Buratti P, Samaja M, Dey S et al. · American journal of physiology. Regulatory, integrative and comparative physiology · 2015PubMed Verified

38. 38.
    ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes

    Brines M, Dunne AN, van Velzen M, Proto PL, Ostenson CG, Kirk RI et al. · Molecular medicine (Cambridge, Mass.) · 2015Clinical TrialPubMed Verified

39. 39.
    Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions

    Thevis M, Thomas A, Schänzer W · Expert review of proteomics · 2014PubMed Verified

40. 40.
    A non-erythropoietic peptide derivative of erythropoietin decreases susceptibility to diet-induced insulin resistance in mice

    Collino M, Benetti E, Rogazzo M, Chiazza F, Mastrocola R, Nigro D et al. · British journal of pharmacology · 2014PubMed Verified

41. 41.
    Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection

    Liu Y, Luo B, Han F, Li X, Xiong J, Jiang M et al. · PloS one · 2014PubMed Verified

42. 42.
    ARA 290 for treatment of small fiber neuropathy in sarcoidosis

    van Velzen M, Heij L, Niesters M, Cerami A, Dunne A, Dahan A et al. · Expert opinion on investigational drugs · 2014ReviewPubMed Verified

43. 43.
    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

    Swartjes M, van Velzen M, Niesters M, Aarts L, Brines M, Dunne A et al. · Molecular pain · 2014PubMed Verified

44. 44.
    Therapeutic effects of nonerythropoietic erythropoietin analog ARA290 in experimental autoimmune encephalomyelitis rat

    Chen H, Luo B, Yang X, Xiong J, Liu Z, Jiang M et al. · Journal of neuroimmunology · 2014PubMed Verified

45. 45.
    Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury

    van Rijt WG, Nieuwenhuijs-Moeke GJ, van Goor H, Ottens PJ, Ploeg RJ, Leuvenink HG · Journal of translational medicine · 2013PubMed Verified

46. 46.
    Editorial

    Tracey KJ · Molecular medicine (Cambridge, Mass.) · 2013PubMed Verified

47. 47.
    ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density

    Dahan A, Dunne A, Swartjes M, Proto PL, Heij L, Vogels O et al. · Molecular medicine (Cambridge, Mass.) · 2013RCTPubMed Verified

48. 48.
    Potential role of erythropoietin receptors and ligands in attenuating apoptosis and inflammation in critical limb ischemia

    Joshi D, Abraham D, Shiwen X, Baker D, Tsui J · Journal of vascular surgery · 2014PubMed Verified

49. 49.
    Erythropoietin-mediated protection in kidney transplantation: nonerythropoietic EPO derivatives improve function without increasing risk of cardiovascular events

    van Rijt WG, van Goor H, Ploeg RJ, Leuvenink HG · Transplant international : official journal of the European Society for Organ Transplantation · 2014ReviewPubMed Verified

50. 50.
    Ketamine does not produce relief of neuropathic pain in mice lacking the β-common receptor (CD131)

    Swartjes M, Niesters M, Heij L, Dunne A, Aarts L, Hand CC et al. · PloS one · 2013PubMed Verified