Cobalt PeptidesResearch Grade

Scientific Reference

ARA-290 (Cibinetide)

Evidence profile: Human Phase 2 evidence

ARA-290, also called cibinetide, is an 11-residue synthetic peptide modelled on the helix B surface of erythropoietin. Erythropoietin is best known as the hormone that drives red blood cell production, but it also acts on other tissues, and ARA-290 was designed to probe that second set of actions without the effect on blood. Its N-terminal glutamine is cyclised to pyroglutamate, which is why it also appears in the literature as pyroglutamate helix B surface peptide. Most studies are in cell and rodent models of nerve injury, inflammation and metabolic disease. It has also been tested in small, early-phase human trials, including in neuropathy associated with sarcoidosis and with diabetes, and human data remain limited.

Mechanism of Action

Erythropoietin acts on red-cell precursors through a homodimer of its receptor (EPOR). A different receptor, proposed to be EPOR paired with the beta-common receptor subunit (CD131), has been suggested to mediate its actions outside the blood-forming system. ARA-290 reproduces the helix B face of erythropoietin, which is thought to engage this proposed complex but not the classical homodimer, and it has been reported not to stimulate red-cell production in animal studies. Cell and rodent work has examined its influence on inflammatory cytokine signalling and apoptosis. The make-up and role of the proposed receptor remain debated.

Molecular Information

  • Type: Synthetic undecapeptide
  • Length: 11 amino acids
  • Molecular weight: 1257.3 g/mol
  • Molecular formula: C51H84N16O21
  • CAS: 1208243-50-8

Published Research

  • Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain

    Culver DA et al. · Investigative ophthalmology & visual science · 2017 · Clinical

    PMID 28475703 — View on PubMed

  • ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes

    Brines M et al. · Molecular medicine (Cambridge, Mass.) · 2015 · Clinical

    PMID 25387363 — View on PubMed

  • ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density

    Dahan A et al. · Molecular medicine (Cambridge, Mass.) · 2013 · Clinical

    PMID 24136731 — View on PubMed

  • Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study

    Heij L et al. · Molecular medicine (Cambridge, Mass.) · 2012 · Clinical

    PMID 23168581 — View on PubMed

  • Managing fatigue in sarcoidosis - A systematic review of the evidence

    Atkins C et al. · Chronic respiratory disease · 2017 · Review

    PMID 27507833 — View on PubMed