Compound reference
ARA-290
Also known as Cibinetide, HBSP, pHBSP
A non-erythropoietic peptide engineered from erythropoietin that selectively activates the innate repair receptor. Small Phase 2 trials show consistent benefit in small-fiber neuropathy, but it remains investigational and unapproved.
- CAS
- 1208243-50-8
- Formula
- C51H84N16O21
- Molar mass
- ≈1,257 g/mol
- Sequence
- 11-residue pyroglutamate helix-B surface peptide (from erythropoietin)
- Half-life
- ≈20 min (subcutaneous), ≈2 min (intravenous) — effects outlast exposure
Investigational; not an approved medicine.
Mode of action
ARA-290 (cibinetide) is an 11-amino-acid peptide modelled on the helix-B surface of erythropoietin (EPO). Its design solves a specific problem: EPO is strongly tissue-protective and anti-inflammatory, but it also drives red-cell production and clotting, which makes it dangerous as a repair drug. ARA-290 keeps the protective half and drops the rest.
It does this by acting only at the "innate repair receptor" (IRR) — a heterodimer of the EPO receptor and the beta-common receptor — rather than the EPO-receptor homodimer that triggers erythropoiesis. Through the IRR it promotes cytoprotection, dampens inflammation, and supports small-nerve-fibre repair. Its plasma half-life is very short (minutes), yet the biological effects last far longer, which is consistent with switching on a repair program rather than occupying a receptor continuously.
Main intended effect
Tissue protection and repair — in clinical work specifically the regeneration of small nerve fibres and relief of neuropathic pain, alongside anti-inflammatory effects.
Areas of interest
The lead indication is small-fibre neuropathy, studied most in sarcoidosis-associated neuropathy and in diabetic painful neuropathy. Preclinically the same innate-repair-receptor mechanism has been explored across kidney, nerve, and inflammatory-injury models, reflecting EPO's broad tissue-protective biology.
Evidence for intended effects
Unlike many research peptides, ARA-290 has a coherent run of controlled Phase 2 trials — though it has not advanced to confirmatory Phase 3 or approval. A randomised pilot in sarcoidosis small-fibre neuropathy improved symptom scores; follow-on trials showed increased corneal small-nerve-fibre density (a structural, disease-modifying readout), including a 64-subject Phase 2b. In type 2 diabetes with painful neuropathy, daily subcutaneous ARA-290 improved neuropathic symptoms along with HbA1c and lipids. The signals are consistent and include objective nerve-regrowth measures, but the trials are small and the program has not delivered a definitive Phase 3.
| Strand | What exists | Tier |
|---|---|---|
| Sarcoidosis small-fiber neuropathy | Randomised pilot + Phase 2b (nerve-fiber density) | Phase 2 (consistent) |
| Diabetic neuropathy | Phase 2 (symptoms + metabolic markers) | Phase 2 |
| Mechanism / tissue protection | IRR pharmacology; preclinical injury models | Established mechanism / preclinical |
Studied amounts (literature dosing context)
The trials used intravenous dosing (e.g. 2 mg three times weekly) and subcutaneous dosing (1, 4, or 8 mg/day in the dose-ranging work). These are study amounts from investigational trials; there is no approved dose, and this page does not provide dosing guidance.
Safety and regulatory status
Across the Phase 2 trials ARA-290 was well tolerated, with no significant adverse effects reported — and by design it avoids EPO's hematocrit and thrombotic risks because it does not stimulate erythropoiesis. That favourable safety record is one of its more notable features.
It remains investigational, however, and is not an approved medicine in any jurisdiction. Material sold online as "ARA-290" or "cibinetide" is an unregulated research compound whose identity and purity are not assured.
Sources
Flipping the molecular switch for innate protection and repair of tissues: long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin
Review (Collino, Thiemermann, Cerami and colleagues, Pharmacology & Therapeutics, 2015) of ARA-290 (pyroglutamate helix B surface peptide, pHBSP) — an 11-amino-acid linear peptide of ~1258 Da derived from the helix B surface of erythropoietin (EPO). It selectively activates the innate repair receptor (IRR), a heterodimer of the EPO receptor and the beta-common receptor, to drive tissue protection and anti-inflammation without stimulating erythropoiesis (it does not act through the EPO-receptor homodimer). Despite a very short plasma half-life (about 2 minutes), it triggers sustained biological effects in animal models and clinical trials.
https://www.sciencedirect.com/journal/pharmacology-and-therapeutics
Targeting the innate repair receptor to treat neuropathy
Review (Dahan, Brines, Niesters, Cerami and colleagues, Pain Reports / Pain, 2016) of ARA290 as an 11-amino-acid selective agonist of the innate repair receptor. It reports ARA290's human pharmacokinetics — an elimination half-life of about 20 minutes after subcutaneous and about 2 minutes after intravenous administration — and summarizes human trial data showing improved neuropathic and autonomic symptoms, quality of life, and corneal small-nerve-fiber regrowth in small fiber neuropathy associated with sarcoidosis or type 2 diabetes, without significant adverse effects.
Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study
Randomized, double-blind pilot trial (Heij and colleagues, Molecular Medicine, 2012) of ARA 290 given as intravenous 2 mg three times weekly for 4 weeks in sarcoidosis patients with small fiber neuropathy. ARA 290 appeared safe and significantly improved the Small Fiber Neuropathy Screening List (SFNSL) score versus placebo. The peptide is designed to activate the innate repair receptor to initiate cytoprotection, anti-inflammation, and healing.
ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density
Blinded, placebo-controlled trial (Dahan and colleagues, Molecular Medicine, 2013) of a daily subcutaneous dose of ARA 290 for 28 days in patients with sarcoidosis-associated small nerve fiber loss. ARA 290 significantly improved neuropathic symptoms, increased corneal small nerve fiber density, altered cutaneous temperature sensitivity, and increased exercise capacity — consistent with a disease-modifying effect via innate-repair-receptor activation rather than simple analgesia.
Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain
Phase 2b, 28-day randomized trial (Culver and colleagues, Investigative Ophthalmology & Visual Science, 2017) in 64 subjects with sarcoidosis-associated small nerve fiber loss and neuropathic pain, testing cibinetide (ARA-290) at 1, 4, or 8 mg/day versus placebo. Acting as an innate-repair-receptor agonist, cibinetide increased small nerve fiber abundance in the cornea and skin — consistent with a disease-modifying rather than purely symptomatic effect.
ARA 290, a non-erythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes
Phase 2 clinical study (Brines and colleagues, Molecular Medicine, 2014) in which subjects with type 2 diabetes and painful neuropathy self-administered subcutaneous ARA 290 (4 mg) daily for 28 days. Treatment improved HbA1c, lipid profiles, neuropathic symptoms (PainDetect score), and corneal nerve fiber density versus the comparator, with no identified safety issues. ARA 290 is an 11-amino-acid peptide modeled on helix B of erythropoietin that interacts selectively with the innate repair receptor.
The erythropoietin analog ARA 290 for treatment of sarcoidosis-induced chronic neuropathic pain
Review (Niesters and colleagues, Expert Opinion on Investigational Drugs, 2013) of ARA 290 as a non-hematopoietic erythropoietin analog acting at the innate repair receptor (a heteromer of the EPO receptor and beta-common receptor), with anti-inflammatory and tissue-protective properties. It summarizes two clinical proof-of-concept studies showing ARA 290 produced greater analgesia than placebo in sarcoidosis-induced chronic neuropathic pain without safety issues.