ARA-290, also catalogued as cibinetide, is an 11-residue peptide modelled on the helix-B external surface of erythropoietin, designed to engage the tissue-protective erythropoietin receptor complex without triggering red blood cell production. That single design decision explains why a molecule derived from a haematopoietic hormone appears almost exclusively in neuroprotection, neuropathic pain and inflammation literature rather than in haematology. This page explains what ARA-290 is, how the sequence was chosen, the receptor logic behind it, what has been published, and how the material is specified and handled in the laboratory.
ARA-290 is supplied as a lyophilized powder for laboratory research only. It is not an approved medicine, and nothing here constitutes guidance for administration to humans or animals.
ARA-290 at a glance
| Property | Value |
|---|---|
| Also known as | Cibinetide; helix-B surface peptide (HBSP) |
| Length | 11 residues |
| Parent molecule | Erythropoietin, helix-B external surface |
| CAS number | 1208243-50-8 |
| Molecular formula | C51H84N14O21 |
| Molecular weight | 1259.34 g/mol |
| Proposed target | EPOR/beta-common receptor heterocomplex (innate repair receptor) |
| Erythropoietic activity | None reported at studied concentrations |
| Physical form | White lyophilized powder, sealed glass vial |
| Sizes supplied | 10 mg, 20 mg |
| Purity specification | ≥99% by RP-HPLC with mass confirmation |
Origin and structure: reading a peptide off a protein surface
Erythropoietin is a four-helix-bundle glycoprotein of about 165 amino acids. Its haematopoietic action runs through a homodimer of the erythropoietin receptor, and the residues responsible for that binding sit on defined faces of helices A and D. From the mid-2000s, a line of work argued that erythropoietin has a second, structurally separable activity — tissue protection — mediated by a heterocomplex pairing the erythropoietin receptor with the beta-common receptor, the shared signalling subunit of the GM-CSF, IL-3 and IL-5 receptors. That complex is often called the innate repair receptor.
ARA-290 was derived by taking the solvent-exposed face of helix B, a region that does not participate in classical receptor binding, and reproducing it as a short linear peptide: pyroglutamate-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser. The N-terminal pyroglutamate is a cyclised glutamine that blocks aminopeptidase attack at the free N-terminus, a common stabilising device in short synthetic peptides.
The design intent is worth stating plainly because it defines the molecule. A researcher studying erythropoietin-mediated tissue protection using the full glycoprotein cannot separate protective signalling from erythropoiesis, rising haematocrit and the cardiovascular confounders that follow. ARA-290 was constructed to remove that confound. It is, in effect, a purpose-built experimental tool, and this is why it is used as a reference agonist for the innate repair receptor.
How ARA-290 is thought to work
The mechanism reported in the literature is selective engagement of the EPOR/beta-common heterocomplex. Downstream, published work describes activation of pathways associated with cell survival and with resolution of inflammation, including JAK2/STAT signalling and PI3K/Akt, together with reduced production of pro-inflammatory mediators in immune cells. Because the beta-common subunit is expressed on macrophages, neurons, endothelium and other non-erythroid tissue, the anatomical distribution of the proposed receptor lines up with the tissues in which the peptide has been studied.
A second strand of mechanistic work concerns the transient receptor potential vanilloid channel TRPV1 and small nerve fibre biology, with reports of ARA-290 influencing nociceptor behaviour and epidermal nerve fibre density in model systems. These accounts are complementary rather than competing, and none of them should be read as established; they are the mechanisms that published investigators have proposed and tested, at the level of cell systems and animal models.
What is comparatively well characterised, and unusual for a research peptide, is the negative result: published studies consistently report no meaningful stimulation of erythropoiesis. For an experimental tool, a reliably absent activity is as informative as a present one.
What research has examined
Small nerve fibre and neuropathic pain models
This is the largest and most distinctive part of the ARA-290 literature. The peptide has been examined in rodent models of neuropathic pain and in human phase 2 clinical studies conducted under its cibinetide designation, including work in sarcoidosis-associated small fibre neuropathy and in type 2 diabetes with neuropathy, with reported endpoints covering corneal nerve fibre measures and patient-reported symptom scores. Those trials concern the investigational drug candidate, not research-grade material sold for laboratory use, and the compound has not received marketing authorisation.
Inflammation and immune modulation
Cell and rodent work has examined macrophage phenotype, cytokine output and markers of inflammatory resolution. This places ARA-290 in the same broad research space as sequences such as KPV, though the entry points differ completely: one works through a receptor heterocomplex, the other through intracellular NF-kappa B signalling.
Ischaemia, organ protection and metabolic models
Preclinical studies have investigated the peptide in models of ischaemia-reperfusion injury across several organ systems and in islet and transplantation models, drawing on the tissue-protection hypothesis that motivated the design. Findings here are rodent and in vitro.
Immune and repair contexts
Laboratories comparing immunomodulatory peptides frequently place ARA-290 alongside thymosin alpha-1, which acts on toll-like receptor signalling and T-cell maturation, or alongside BPC-157 in repair models. The comparison is instructive precisely because the mechanisms have nothing in common.
Forms and sizes we supply
ARA-290 is stocked as a lyophilized powder in 10 mg (USD 100) and 20 mg (USD 180) sealed vials with crimped stoppers. At 1259.34 g/mol, a 10 mg vial contains roughly 7.9 micromoles — a moderate molar quantity that sits between the very high yields of tripeptides and the low yields of full-length proteins. Related material is grouped under anti-inflammatory peptides and, for immune-directed work, immune peptides.
Reconstitution and storage in a laboratory context
Reconstitution is a concentration calculation. A 10 mg vial reconstituted with 2 mL of bacteriostatic water gives 5 mg/mL, equivalently 5,000 mcg/mL; 0.1 mL (10 units on a U-100 syringe) contains 500 mcg. In molar terms, 5 mg/mL of a 1259.34 g/mol peptide is approximately 3.97 mM, which is the number that matters when preparing nanomolar or micromolar working solutions for cell assays.
The peptide dissolves readily in aqueous buffer. Diluent is added slowly against the vial wall rather than jetted onto the cake, and the vial is swirled rather than shaken, since mechanical agitation promotes aggregation at air-liquid interfaces. Lyophilized vials are stored at −20 °C protected from light; reconstituted solution is refrigerated and aliquoted so repeated warming is avoided. Step-by-step method is in the reconstitution guide, and temperature and stability detail in the storage guide.
Purity, COA and how to read one
Each lot is purified by reversed-phase HPLC to at least 99% with mass confirmation, and the certificate is matched to the lot number on the vial. For an 11-residue peptide with an N-terminal pyroglutamate, two checks deserve particular attention. First, the observed mass should be consistent with 1259.34 g/mol; an unmodified glutamine at the N-terminus would show 17 Da higher, so mass is the direct evidence that the pyroglutamate closure actually happened. Second, this sequence contains asparagine and serine residues that can deamidate or degrade under poor storage, and the HPLC trace is where shoulder peaks from such degradation appear. Read the chromatogram, not only the summary figure. Our COA reading guide walks through real traces and explains what net peptide content means relative to gross vial weight.
Regulatory status
Cibinetide has been the subject of clinical investigation but holds no marketing authorisation in the United States or the European Union, and ARA-290 is not an approved medicine, a dietary supplement or a compounded preparation in general availability. Material supplied here is research use only, intended for in-vitro and preclinical laboratory work by qualified investigators. Published human trial data describe the investigational drug candidate under controlled conditions; they do not transfer to research-grade material, and no therapeutic claim is made for it.
Related peptides and further reading
For the wider landscape of repair-directed research peptides and how investigators choose between mechanisms, see the healing and recovery research overview. Within this catalogue, KPV, VIP and thymosin alpha-1 represent three further and mechanistically unrelated approaches to inflammation research; ARA-290 remains the only one built specifically to isolate a receptor heterocomplex from its parent hormone's dominant activity.