Summary

ARA-290 (cibinetide) is a synthetic 11-amino-acid peptide derived from the helix B domain of erythropoietin (EPO). It activates the innate repair receptor (a complex of the EPO receptor and CD131/beta-common receptor) to promote tissue repair and reduce inflammation without stimulating erythropoiesis. ARA-290 has been investigated in Phase II clinical trials for small fibre neuropathy, sarcoidosis, and other conditions, with evidence of symptom improvement.

Mechanism

ARA-290 activates the innate repair receptor (IRR), a heterocomplex of the EPO receptor and the beta-common receptor (CD131). This triggers anti-apoptotic (JAK2/STAT3) and tissue repair (PI3K/Akt) signalling pathways without stimulating erythropoiesis, distinguishing it from recombinant EPO. The tissue-protective effects include reduced apoptosis, reduced inflammation, and promotion of tissue repair across multiple organ systems.

Evidence base

Evidence Grading: Moderate

ARA-290 has reached Phase II human clinical trials.

Clinical evidence:

  • Brines et al. (2013): Phase II RCT in sarcoidosis-associated small fibre neuropathy — significant improvement in neuropathic pain and nerve fibre function over 28 days.
  • Brines et al. (2014): Phase II trial in painful diabetic neuropathy — improvements in pain scores and quality of life.
  • Safety: No significant erythropoietic effects (no haematocrit increases), generally well-tolerated.

Preclinical evidence:

  • Brines et al. (2008): Tissue-protective effects in models of cardiac ischaemia, stroke, and kidney injury.
  • Cerami et al. (2019): Review describing the innate repair receptor as a disease-agnostic tissue protection target.

Gap: Phase III trials have not been completed or published. Evidence is insufficient for regulatory approval.

Protocols

Research-Only Protocols

No approved human dosing protocols exist outside clinical trial settings.

In published Phase II trials:

  • Route: Subcutaneous injection
  • Dose: 2–4 mg daily
  • Duration: 28 days
  • Monitoring: Complete blood counts, renal function, pain scores

These were administered under clinical trial conditions with safety oversight.

ARA-290 is not a licensed medicine in the UK and is not a controlled substance. It falls into a grey area: it may be sold for bona fide research purposes but is not MHRA-approved for human therapeutic use. It has been investigated under clinical trial authorisations. See our UK legal status guide for further detail.

Vendor notes

ARA-290 may be available from select UK research peptide suppliers. Request a Certificate of Analysis (COA) verifying purity (typically ≥98%). See the vendor vetting guide for evaluation criteria.

References

  1. Brines M, et al. "ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes." Molecular Medicine. 2014;20:658-669.
  2. Brines M, et al. "A small peptide mimetic of the helix B domain of erythropoietin is tissue-protective in models of lung and pancreatic injury." FASEB Journal. 2013;27(8):3154-3167.
  3. Brines M, et al. "Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin." PNAS. 2008;105(31):10925-10930.
  4. Cerami A, et al. "ARA-290 and the innate repair receptor: a disease-agnostic approach to tissue protection." Int J Mol Sci. 2019;20(4):886.