ARA-290
From PeptidePlaza, the free peptide reference · Entry #029 · Recovery · Hand-curated entry · Editorial standards
ARA-290 (also known as Cibinetide, ARA 290, Helix B surface peptide) is a recovery research peptide. A non-erythropoietic peptide derived from erythropoietin (EPO) that activates the innate repair receptor. Studied in Phase 2 clinical trials for neuropathy, inflammation, and tissue protection without EPO’s red-cell effects.
ARA-290 (cibinetide) is an 11-amino-acid peptide derived from the helix-B domain of erythropoietin (EPO). It selectively activates the innate repair receptor (a heterocomplex of EPO receptor and β-common receptor) while having no erythropoietic activity — meaning it does not stimulate red blood cell production. ARA-290 activates tissue-protective and anti-inflammatory signaling cascades, and has completed Phase 2 clinical trials for sarcoidosis-associated small fiber neuropathy, diabetic macular edema, and diabetic neuropathy, showing improvements in neuropathic symptoms and corneal nerve fiber density. It is also studied for islet transplantation and ischemic conditioning.
1 Mechanism of action
Activates the innate repair receptor (EPOR/βcR heterodimer), triggering JAK2/STAT and PI3K/Akt anti-apoptotic and anti-inflammatory signaling in neurons, endothelial cells, and immune cells, without the JAK2-mediated erythropoiesis of EPO.
Primary targets: Innate Repair Receptor (EPOR/βcR)
2 Reported effects
Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.
2.1 Reported benefits
- Reduced neuropathic pain in Phase 2 trials
- Improved corneal nerve fiber density (nerve regeneration)
- Anti-inflammatory without erythropoiesis
- Protects islet grafts and ischemic tissue in models
2.2 Side effects
- Injection site reactions
- Headache
- Mild gastrointestinal symptoms
- Generally well tolerated in trials
3 Chemical and physical properties
| CAS number | 936727-05-8 |
|---|---|
| Molar mass | ~1268 g/mol |
| Purity (typical) | >98% |
| Half-life | ~30 minutes (SC); effects on nerve fiber density persist weeks |
| Storage | −20 °C, lyophilised powder, desiccated |
| Solubility | Sterile water / bacteriostatic water |
| Receptors / targets | Innate Repair Receptor (EPOR/βcR) |
3.1 Amino acid sequence
pH-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (helix B EPO-derived)
4 Research dosages
4 mg SC 3×/week in published Phase 2 protocols.
5 Research studies (6)
- ARA 290 for treatment of small fiber neuropathy in sarcoidosis.
Expert opinion on investigational drugs (2014) · ReviewINTRODUCTION: Painful peripheral neuropathy is a common, difficult-to-treat complication associated with a variety of diseases, including diabetes mellitus and sarcoidosis. - A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema.
Journal of clinical medicine (2020) · ReviewPURPOSE: Evaluating the effects of cibinetide in diabetic macular edema (DME). - Early monocyte modulation by the non-erythropoietic peptide ARA 290 decelerates AD-like pathology progression.
Brain, behavior, and immunity (2022) · ReviewAlzheimer's disease (AD) pathology is characterized by amyloid-β (Aβ) deposition and tau hyper-phosphorylation, accompanied by a progressive cognitive decline. - Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis.
Scientific reports (2017) · ReviewTwo distinct forms of the erythropoietin receptor (EPOR) mediate the cellular responses to erythropoietin (EPO) in different tissues. - Improvement of Islet Allograft Function Using Cibinetide, an Innate Repair Receptor Ligand.
Transplantation (2020) · ReviewBACKGROUND: During intraportal pancreatic islet transplantation (PITx), early inflammatory reactions cause an immediate loss of more than half of the transplanted graft and potentiate subsequent allograft rejection. - Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation.
Cell transplantation (2021) · ReviewDuring intra-portal pancreatic islet transplantation (PITx), innate immune reactions such as the instant blood mediated inflammatory reaction (IBMIR) cause an immediate loss of islets.
6 Safety and risk profile
6.1 Regulatory status
ARA-290 is currently classified as Phase 2 clinical trials. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.
Safety score: 62/100 — moderate concern. Derived from clinical data volume, known risks and regulatory status.
6.2 Contraindications
Conditions and populations in which use is contraindicated:
- Pregnancy or lactation
- Known hypersensitivity to EPO-derived peptides
6.3 Drug interactions
| Drug or class | Interaction | Risk |
|---|---|---|
| Erythropoietin / ESAs | Additive receptor pathway activation possible — monitor hematocrit. | Low |
6.4 Long-term risks
- Limited long-term data
- Effects of chronic innate-repair-receptor stimulation unknown
6.5 Research best practices
- Store lyophilized at −20 °C
- Reconstitute with saline; use promptly
- Track neuropathic symptom scores and nerve metrics in studies
7 Frequently asked questions
- How is ARA-290 different from EPO?
- ARA-290 is the helix-B fragment of EPO. It binds the innate repair receptor (EPOR/βcR) to provide tissue protection and anti-inflammatory effects, but it does not stimulate red blood cell production — no erythropoiesis.
- What clinical evidence exists?
- Phase 2 trials in sarcoidosis small fiber neuropathy showed reduced neuropathic pain and improved corneal nerve fiber density. Trials in diabetic macular edema and diabetic neuropathy have also been conducted.
- How is it dosed in trials?
- Phase 2 protocols used 4 mg subcutaneous three times per week (e.g., 4 mg SC 3×/week) over 4–12 weeks.
8 References
- ARA 290 for treatment of small fiber neuropathy in sarcoidosis. PubMed (2014). van Velzen M, et al.. View source
- A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema. PubMed (2020). Lois N, et al.. View source
- Early monocyte modulation by the non-erythropoietic peptide ARA 290 decelerates AD-like pathology progression. PubMed (2022). Al-Onaizi MA, et al.. View source
- Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis. PubMed (2017). Nairz M, et al.. View source
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