ARA-290 12mg

ARA-290 (Cibinetide) — Non-Erythropoietic Erythropoietin-Derived Tissue-Protective Peptide

Chemical and Biochemical Characteristics

• Peptide Name: ARA-290 (Cibinetide)

• Amino Acid Sequence: ZEQLERALNSS

• Molecular Formula: C₅₁H₈₄N₁₆O₂₁

• Molecular Weight: 1257.3 g/mol

• CAS Number: 1208243-50-8

• PubChem CID: 91810664

• Synonyms: Cibinetide, PH-BSP, Non-hematopoietic EPO analogue

• Peptide Class: Tissue-protective and anti-inflammatory erythropoietin derivative

Overview

ARA-290 (Cibinetide) is a synthetic peptide derived from the β-helix domain of erythropoietin (EPO), designed to retain EPO’s tissue-protective and neuroregenerative properties while eliminating its erythropoietic and pro-thrombotic effects.
It selectively activates the EPOR-CD131 heteroreceptor complex — known as the tissue-protective receptor (TPR) — triggering anti-apoptotic, anti-inflammatory, and pro-regenerative signaling cascades without stimulating red blood cell production.

Through this mechanism, ARA-290 represents a promising research tool for investigating neuropathic pain, microvascular repair, inflammatory regulation, and tissue regeneration.

Mechanism of Action

ARA-290 binds to the EPOR-CD131 heteroreceptor rather than the classical homodimeric erythropoietin receptor (EPOR-EPOR).
This unique interaction initiates a distinct downstream cascade that:

• Inhibits NF-κB–driven inflammatory gene expression;

• Reduces release of TNF-α, IL-6, and IL-12;

• Enhances cell survival and mitochondrial protection;

• Promotes angiogenesis and endothelial repair;

• Restores small nerve fiber density in peripheral tissues【1】【2】【3】.

The result is a highly selective activation of cytoprotective and neuroprotective pathways without the hematologic side effects of erythropoietin.

Microvascular and Endothelial Protection

Preclinical studies demonstrate that ARA-290 enhances endothelial progenitor proliferation, migration, and survival.
In ischemic retinal models, it significantly improved microvascular regeneration and endothelial integrity, preventing apoptosis of retinal cells【4】.
ARA-290 also promotes homing of circulating endothelial colony-forming cells (ECFCs) to damaged vascular sites, suggesting potential for vascular repair and ischemic recovery research.

Immunomodulation and Cytokine Regulation

ARA-290 exerts strong anti-inflammatory and immunomodulatory effects through the tissue-protective receptor (TPR) expressed on macrophages, dendritic cells, and T-lymphocytes.
By modulating these immune cells, ARA-290:

• Decreases secretion of pro-inflammatory cytokines (TNF-α, IL-6, IL-12);

• Suppresses macrophage activation while preserving resident immune surveillance;

• Limits chemokine-driven infiltration into inflamed tissue;

• Modifies antigen presentation to balance adaptive immunity【5】【6】.

Such properties make ARA-290 a valuable model compound for studying autoimmune modulation, transplantation tolerance, and inflammatory bowel conditions.

Neuroprotective and Analgesic Research

ARA-290 has been extensively studied for neuropathic pain — both peripheral and central.
In models of diabetic neuropathy and sarcoidosis-related small fiber neuropathy, it reduced pain intensity and improved intraepidermal nerve fiber density, indicating regeneration of small sensory fibers【7】【8】.
Mechanistically, ARA-290 also interacts with TRPV1 (capsaicin receptor) channels, reducing neurogenic inflammation and pain hypersensitivity.
Clinical trials (Phase II–III) have shown improved neuropathic symptom scores and corneal nerve fiber abundance, marking a breakthrough in non-opioid pain modulation research【9】【10】.

Autoimmune and Inflammatory Models

ARA-290 (Cibinetide) has demonstrated benefits in experimental models of systemic lupus erythematosus (SLE) and colitis, where it reduced autoantibody titers (ANA, anti-dsDNA), preserved renal tissue, and attenuated NF-κB signaling【11】【12】.
This positions ARA-290 as a next-generation selective immunomodulator, acting through innate repair receptors rather than broad immunosuppression.

Tissue Protection and Wound Healing

By activating EPOR-CD131, ARA-290 enhances angiogenesis, reduces fibrosis, and accelerates wound closure in diabetic models【13】.
Unlike erythropoietin, it does not increase hematocrit or promote thrombosis, maintaining a favorable safety profile for long-term experimental use.

Clinical Development

ARA-290 (Cibinetide) has completed Phase II trials for diabetic neuropathy and is undergoing Phase III evaluation for sarcoidosis-related small fiber neuropathy.
It was granted Orphan Drug Designation by the U.S. FDA (2016) for neuropathic pain associated with sarcoidosis, highlighting its relevance in neuroimmune research.

Other ongoing investigations explore its use in ischemic tissue recovery, chronic fatigue, long COVID, and autoimmune disorders.

Summary

ARA-290 (Cibinetide) is a non-erythropoietic EPO-derived peptide that activates tissue-protective pathways to regulate inflammation, support microvascular integrity, and restore neural function.
Its selective receptor targeting allows exploration of neuroprotection, angiogenesis, and immune regulation without hematologic side effects.

This peptide is intended solely for scientific and educational research purposes and is not approved for human therapeutic use.

Selected References

1. Brines M. et al. ARA-290 improves metabolic control and neuropathic symptoms in diabetic patients. Mol Med, 2015; 20: 658–666. PubMed

2. O’Leary O.E. et al. Cibinetide enhances vasoreparative potential in ischemic retina. Exp Eye Res, 2019; 182: 144–155. PubMed

3. Hache G. et al. ARA-290 improves angiogenic potential of endothelial progenitors. Shock, 2016; 46(4): 390–397. PubMed

4. Watanabe M. et al. ARA-290 inhibits macrophage activation and protects transplanted islets. Transplantation, 2016; 100(3): 554–562. PubMed

5. Peng B. et al. Erythropoietin and its derivatives in immune regulation. Cell Death Dis, 2020; 11(2): 79. PubMed

6. Yan L. et al. ARA-290 attenuates renal allograft injury via NF-κB pathway. Transplant Proc, 2018; 50(5): 1575–1582. PubMed

7. Culver D.A. et al. Cibinetide improves corneal nerve fiber abundance in sarcoidosis neuropathy. Invest Ophthalmol Vis Sci, 2017; 58(6): BIO52–BIO60. PubMed

8. van Velzen M. et al. ARA-290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opin Investig Drugs, 2014; 23(4): 541–550. PubMed

9. Nairz M. et al. Cibinetide dampens innate immune cell functions and ameliorates colitis. Sci Rep, 2017; 7(1): 13012. PubMed

10. Huang B. et al. EPO-derived peptide protects mice from lupus-like autoimmunity. J Cell Mol Med, 2018; 22(7): 3330–3339. PubMed

11. Bitto A. et al. EPOR-βcR activation by Cibinetide enhances diabetic wound healing. Biochim Biophys Acta Mol Basis Dis, 2018; 1864(2): 632–639. PubMed

Product Use: THIS PRODUCT IS STRICTLY FOR SCIENTIFIC RESEARCH PURPOSES ONLY. It should only be used in laboratory settings. All product information on this website is provided solely for educational purposes. The law strictly prohibits introducing this product into the body of humans or animals. Only licensed professionals should handle this product. This product is not a drug, food, or cosmetic and should not be improperly classified or used as such.