ARA-290 (cibinetide)

ARA-290 (cibinetide) is an 11-residue synthetic peptide modeled on a surface region of erythropoietin. It was designed to engage tissue-protective signaling without stimulating red blood cell production and has been studied in early clinical trials of neuropathy.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

ARA-290, also known by the international nonproprietary name cibinetide, is a short peptide derived from the three-dimensional structure of erythropoietin (EPO). EPO is best known as the hormone that drives red blood cell production, but it also has tissue-protective effects in experimental models. Researchers sought to separate these two activities, and ARA-290 was engineered from a portion of EPO's helix B that faces away from the classical EPO receptor binding site, with the aim of retaining protective signaling while avoiding erythropoietic effects.

The compound has been studied in rodent models of nerve injury, inflammation and metabolic disease, and in small human trials, mainly in small fiber neuropathy associated with sarcoidosis and in neuropathy associated with type 2 diabetes. These trials were early-phase and relatively small, with symptom scores and corneal nerve measures among the outcomes. Larger confirmatory trials have not been reported, so the human evidence remains limited and the compound is regarded as investigational.

Structure

ARA-290 is a linear 11-residue peptide with the sequence pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (pEQLERALNSS). The N-terminal residue is pyroglutamate, a cyclized form of glutamine or glutamic acid that blocks the free N-terminal amine and is thought to improve resistance to aminopeptidases. The sequence corresponds to a modified segment of the aqueous face of helix B of human erythropoietin. It contains no cysteine, methionine or tryptophan. Research material is generally supplied as a lyophilized salt, commonly acetate or trifluoroacetate.

Mechanism

ARA-290 is proposed to act through the so-called innate repair receptor, described as a heteromeric complex of the EPO receptor and the β common receptor (CD131), which is distinct from the EPO receptor homodimer that mediates erythropoiesis. Signaling through this complex has been linked in experimental studies to anti-inflammatory and anti-apoptotic effects in injured tissue.

The receptor model and downstream pathways are based mainly on preclinical work and have not been fully characterized in people. In animal and cell studies, ARA-290 did not stimulate red blood cell production, consistent with its design, but how its experimental effects on nerve function and inflammation arise remains under investigation.

Research

Small fiber neuropathy in sarcoidosis

The most developed clinical work with ARA-290 is in small fiber neuropathy associated with sarcoidosis, a condition in which damage to small sensory and autonomic nerve fibers causes pain and other symptoms. Small randomized, placebo-controlled phase 2 studies assessed symptom questionnaires, functional measures and corneal nerve fiber density measured by corneal confocal microscopy. Investigators reported changes in some outcomes, but the trials were small and short, and the findings have not been confirmed in a larger phase 3 program.

Diabetic neuropathy and metabolic measures

A small randomized trial in people with type 2 diabetes and painful neuropathy examined neuropathic symptoms, corneal nerve measures and markers of metabolic control. The authors reported improvements in some measures relative to placebo. Rodent studies in diabetic and diet-induced metabolic models had earlier explored effects on nerve function, glucose handling and inflammation. The clinical data are early-phase and should be regarded as preliminary.

Preclinical injury and inflammation models

In rodent models, ARA-290 and related helix B peptides have been examined after nerve injury, ischemia-reperfusion injury, and in inflammatory and pain models. These studies are the basis for describing the peptide as tissue-protective. As with many repair-signaling peptides, the animal experiments vary in design and endpoints, and their relevance to human disease has not been established. Many of these experiments came from groups involved in developing the compound.

Evidence quality

The ARA-290 literature combines a coherent design rationale with a modest number of small human trials, largely from a limited group of investigators and the developing company. Effect sizes, durability and safety over longer periods have not been characterized in large controlled studies. The compound is best described as an investigational peptide with early clinical evidence in neuropathy and broader preclinical evidence in injury models.

Regulatory status

ARA-290 (cibinetide) is not approved by the FDA for any use and remains investigational. It is not a recognized substance for pharmacy compounding in the US. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A certificate of analysis should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page, and report reverse-phase HPLC purity with the chromatogram. The N-terminal pyroglutamate is a key quality point: material with an open-chain N-terminal glutamine or glutamate differs in mass (pyroglutamate formation from glutamine involves loss of ammonia, about 17 Da), so the COA should confirm the cyclized form. Deamidation of the Gln or Asn residues (+1 Da) is a possible degradation route. The counter-ion and net peptide content should be stated.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized ARA-290 sealed at -20 °C or colder, protected from light and moisture, and let vials reach room temperature before opening. The sequence lacks cysteine, methionine and tryptophan, so oxidation is a minor concern, but the asparagine and glutamine residues can deamidate in solution, particularly at neutral to basic pH and higher temperatures. Prepare solutions for lab use in sterile water or buffer, keep them refrigerated for short-term work, aliquot for longer storage at -20 °C or below, and avoid repeated freeze-thaw cycles.

Download the ARA-290 (cibinetide) data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• BPC-157

  BPC-157 is a synthetic 15-amino-acid peptide whose sequence was derived from a protein fraction of gastric juice. It is studied mainly in rodent models of gastrointestinal, tendon and soft-tissue injury and is not approved for any use.

• Thymosin β4

  Thymosin β4 is a naturally occurring 43-amino-acid peptide that binds monomeric actin and is abundant in many cell types. It has been studied in animal models of tissue repair and in human trials of ophthalmic and topical formulations, and is not approved.

• KPV

  KPV is the tripeptide lysine-proline-valine, the C-terminal sequence of alpha-melanocyte-stimulating hormone. It is studied for anti-inflammatory effects in cell and rodent models, particularly of intestinal inflammation, and is not approved for any use.

• VIP (vasoactive intestinal peptide)

  Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide of the secretin-glucagon family that acts on VPAC1 and VPAC2 receptors. It regulates smooth muscle, secretion and immune function, and synthetic VIP (aviptadil) has been studied clinically.

References

1. PubMed: all indexed literature on ARA-290 (cibinetide)
2. ClinicalTrials.gov: registered studies mentioning ARA-290 (cibinetide)