ARA-290 (Cibinetide / EPO-Derived Tissue-Protective Peptide)
Also Known AsCibinetide · ARA 290 · pHBSP
Developed by Araim Pharmaceuticals based on the tissue-protective domain of erythropoietin (EPO). ARA-290 is a linear 11-amino acid peptide derived from the B-helix surface of EPO that selectively activates the innate repair receptor (IRR), a heterodimer of EPOR and beta common receptor (betaCR/CD131), without stimulating erythropoiesis. This separation of tissue protection from red blood cell production addresses the thrombotic risk of full-length EPO.
Gln-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-SerHow ARA-290 Works
Innate Repair Receptor (IRR) Activation
ARA-290 selectively binds the innate repair receptor, a heterocomplex of EPOR and betaCR (CD131) expressed on damaged and inflamed tissues. Unlike full-length EPO, it does not activate the classical homodimeric EPOR responsible for erythropoiesis. IRR activation triggers JAK2-STAT5 signaling in a tissue-protective rather than erythropoietic context.
Anti-Inflammatory Cytokine Modulation
IRR signaling suppresses NF-kappaB-dependent pro-inflammatory gene transcription, reducing TNF-alpha, IL-1beta, and IL-6 production. Simultaneously, it upregulates anti-inflammatory mediators including IL-10 and TGF-beta, promoting resolution of inflammation in damaged tissues.
Small Nerve Fiber Repair
ARA-290 promotes regeneration of intraepidermal nerve fibers (IENFs) through IRR-mediated signaling on Schwann cells and dorsal root ganglion neurons. Clinical studies demonstrated increased corneal nerve fiber density and skin biopsy nerve fiber counts in neuropathy patients.
Anti-Apoptotic Signaling
IRR activation induces PI3K/Akt-dependent cell survival signaling, upregulating Bcl-XL and inhibiting caspase-3 activation in metabolically stressed cells. This protects neurons, cardiomyocytes, and renal tubular cells from ischemia-reperfusion and inflammatory injury.
Published Research
Diabetic Neuropathy & Small Fiber Neuropathy
StrongPhase II clinical trials in type 2 diabetic patients with small fiber neuropathy demonstrated statistically significant improvements in corneal nerve fiber density, neuropathic pain scores (NRS), and patient-reported quality of life after 28 days of subcutaneous ARA-290. Intraepidermal nerve fiber regeneration was confirmed by serial skin biopsy.
Sarcoidosis-Associated Neuropathy
ModerateA phase II trial in sarcoidosis patients with small fiber neuropathy demonstrated reduced neuropathic symptoms, decreased fatigue scores (FAS), and improved corneal nerve fiber morphology. The anti-inflammatory and nerve-regenerative dual mechanism addresses both the underlying granulomatous inflammation and the neuropathic sequelae.
Metabolic Syndrome & Insulin Sensitivity
ModerateClinical studies report improvements in HbA1c, insulin sensitivity (HOMA-IR), and cholesterol profiles in diabetic patients treated with ARA-290. The metabolic benefits may be secondary to reduced systemic inflammation and improved autonomic nerve function regulating metabolic homeostasis.
Myocardial Ischemia-Reperfusion Injury
PreclinicalPreclinical models demonstrate reduced infarct size, improved ejection fraction, and decreased cardiomyocyte apoptosis with ARA-290 administration peri-infarction. The IRR is upregulated on stressed cardiomyocytes, providing a therapeutic window for intervention after ischemic insult.
Chronic Kidney Disease
PreclinicalEarly preclinical data show renoprotective effects of ARA-290 in ischemia-reperfusion and cisplatin-induced nephrotoxicity models. Renal tubular cell apoptosis was reduced, and inflammatory infiltration was attenuated. The IRR is constitutively expressed on renal tubular epithelium, supporting tissue-specific therapeutic potential.
Safety Profile
ARA-290 has been well tolerated in multiple phase I/II clinical trials involving over 300 subjects. No erythropoietic stimulation (hemoglobin/hematocrit changes) has been observed, confirming selectivity for the IRR over the classical EPOR. Injection-site reactions were the most common adverse event. No thrombotic events, cardiovascular adverse events, or dose-limiting toxicities were reported.
Handling & Storage
Reconstitute with bacteriostatic water. Direct gentle stream along vial wall — do not shake. Store reconstituted solution at 2-8°C and use within 28 days. Lyophilized powder stable at -20°C for 24+ months. ARA-290 is chemically stable and does not require light protection.
Peer-Reviewed Literature
- 1
Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin
Brines M, Patel NSA, Villa P, et al.
- 2
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 Bruggen N, et al.
- 3
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, et al.
- 4
The receptor that tames the innate immune response
Brines M, Cerami A.
ARA-290 FAQ
What is ARA-290?
ARA-290 (also known as cibinetide) is an 11-amino acid peptide engineered from the tissue-protective domain of erythropoietin (EPO). It selectively activates the innate repair receptor (EPOR/betaCR heterodimer) without stimulating red blood cell production, providing tissue-protective and nerve-regenerative properties without the thrombotic risks of full-length EPO.
How does ARA-290 differ from EPO?
Full-length EPO activates both the classical homodimeric EPOR (driving erythropoiesis) and the heterodimeric innate repair receptor (driving tissue protection). ARA-290 selectively activates only the innate repair receptor. This means it provides neuroprotective and anti-inflammatory effects without increasing hemoglobin, hematocrit, or thrombotic risk.
What clinical evidence exists for ARA-290 in neuropathy?
Phase II trials demonstrated improved corneal nerve fiber density, reduced neuropathic pain scores, and increased intraepidermal nerve fiber counts in patients with diabetic and sarcoidosis-associated small fiber neuropathy. These are the first clinical demonstrations of nerve fiber regeneration in neuropathy patients.
What is the purity of G26x Peptides ARA-290?
Our ARA-290 is 99%+ purity, independently verified by Janoshik Analytical with a full Certificate of Analysis (COA) available for each batch. It is supplied as a lyophilized powder manufactured under GMP-adjacent conditions.
How should ARA-290 be stored?
Lyophilized ARA-290 should be stored at -20°C for long-term storage (stable for 24+ months). Once reconstituted with bacteriostatic water, store at 2-8°C and use within 28 days. ARA-290 is chemically stable and does not require special light protection.
ARA-290 Products
All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.
ARA-290
16mgNerve repair peptide — activates your body's innate repair receptor to heal damaged nerves, reduce neuropathic pain, and restore sensation without immunosuppression.
- Tissue-protective without immunosuppressive effects
- Repairs nerve damage in neuropathy models
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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.