ARA-290 (cibinetide) is an 11-amino-acid peptide built from the helix B surface of erythropoietin, studied in small fiber neuropathy and type 2 diabetes. This page sets out the whole published human record — four randomized trials in patients and one randomized study in healthy volunteers, their sizes, their doses and their confidence intervals — for educational use only, not medical advice.
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ARA-290 Guide: Available Now
Educational use only — not medical advice. This guide summarizes information reported in published research and community practice for educational purposes. It is not medical advice and not a recommendation to use any compound. Any doses, schedules, or combinations shown are examples of what has been reported, not instructions for you. Many peptides described here are research compounds that are not FDA-approved for the uses discussed and may be investigational or restricted. Effects, risks, and legal status vary; individual needs and results vary. Consult a qualified, licensed healthcare professional before making any decision. Do not use this content to diagnose, treat, or dose yourself.
ARA-290 at a glance
What it is
Cibinetide, also written ARA-290 or pHBSP (pyroglutamate helix B surface peptide): 11 residues, pyroGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser. PubChem CID 91810664, C51H84N16O21, 1257.3 g/mol, CAS 1208243-50-8
Researched for
Small fiber neuropathy in sarcoidosis, neuropathic pain, and metabolic control in type 2 diabetes
The whole human record
Five randomized published studies. Four are trials in patients: 22 sarcoidosis patients (PMID 23168581), a 28-day daily study in sarcoid small-fiber loss (PMID 24136731), a type 2 diabetes study (PMID 25387363), and a 64-participant phase 2b (PMID 28475703). The fifth is a single-dose study in 36 healthy volunteers (PMID 26431906). No phase 3 exists
The doses those trials used
1, 4 or 8 mg once daily by subcutaneous injection in the phase 2b; 4 mg daily in the diabetes study; and 2 mg intravenously three times weekly in the first sarcoidosis trial
More was not better, in the trial's own numbers
Placebo-corrected change in corneal nerve fiber area at day 28 was 109 (95% CI -429 to 647) at 1 mg, 697 (159 to 1236, P = 0.012) at 4 mg, and 431 (-130 to 992) at 8 mg. Only the middle dose separated from placebo
Registry record
Four registered trials name cibinetide or ARA-290 as the intervention: NCT02039687 (Araim, completed, 64), NCT02070783 (Leiden, healthy volunteers, completed, 36), NCT01933529 (24, status listed as unknown) and NCT06626971 (Belfast, diabetic macular oedema, terminated with 9 enrolled)
Plasma half-life (corrected on this page)
No human pharmacokinetic study of cibinetide is indexed in PubMed. The "on the order of minutes" figure this page used to publish traces to no measurement and is withdrawn
What is documented instead
That the biological effect outlasts the plasma exposure: the mechanism is receptor-mediated repair signaling rather than a sustained blood level, which is how a short-lived peptide supports a once-daily schedule (PMID 25728128)
Design rationale
It does not bind the homodimeric EPO receptor that drives red-cell production; it targets the innate repair receptor, a heterocomplex expressed on injured tissue. Separating tissue protection from erythropoiesis, and therefore from EPO's thrombotic risk, is the whole point of the molecule
Healthy volunteers: one published study
One randomized, double-blind study gave a single dose of ARA-290 or placebo to 36 healthy volunteers and tested how they processed emotions a week later: some measures shifted, mood did not (PMID 26431906; registered as NCT02070783). Every other published human dose comes from a patient population with an active disease process. (Corrected 4 October 2026: this row previously said no healthy-volunteer study existed.)
Regulatory status
Investigational. Not FDA-approved for any indication; research use only
Educational reference. This page does not publish dose ranges or reconstitution arithmetic.
What it is / mechanism
ARA-290 is a short peptide engineered from the helix B region of erythropoietin — 11 residues, pyroGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser, PubChem CID 91810664, C51H84N16O21, 1257.3 g/mol, CAS 1208243-50-8, and known in the literature as cibinetide or pHBSP. Its design addresses a specific problem: erythropoietin has well-documented tissue-protective effects, but using EPO itself for that purpose also stimulates red-blood-cell production and raises thrombotic risk. ARA-290 was built to separate the two. It does not bind the classical homodimeric EPO receptor that drives erythropoiesis; instead it selectively activates the innate repair receptor, a heterocomplex of the EPO receptor and beta-common receptor subunits that normal tissue does not express but injury and inflammation rapidly induce. Published research describes activation of this receptor as dampening pro-inflammatory signaling and supporting nerve-fiber repair without haematopoietic activity. That selectivity is the central rationale for the molecule, and it is also why its efficacy trials enrolled patients with an active injury process: the receptor it targets is not usually there to be activated.
Researched effects
The published human record is four randomized trials in patients and one randomized single-dose study in 36 healthy volunteers (PMID 26431906, 2015), which tested emotional processing and found no change in mood. The patient trials are worth reading as a sequence rather than as a single result. The first (PMID 23168581, 2012) was a double-blind placebo-controlled pilot in 22 sarcoidosis patients with small fiber neuropathy symptoms — 12 on ARA-290 and 10 on placebo — dosed 2 mg intravenously three times weekly for four weeks. The second (PMID 24136731, 2013) moved to 28 days of daily subcutaneous dosing in sarcoidosis-associated small nerve fiber loss and reported improved neuropathic symptoms alongside increased corneal nerve fiber density. The third (PMID 25387363, 2015) took 4 mg self-administered subcutaneously daily for 28 days into type 2 diabetes with painful neuropathy, following participants a further month off treatment and reporting improvement in HbA1c and lipid profile across the 56-day observation. The fourth and largest (PMID 28475703, 2017) was a 64-participant phase 2b in sarcoid-associated small nerve fiber loss, comparing 1, 4 and 8 mg daily against placebo with change in corneal nerve fiber area at day 28 as the primary endpoint. These are findings in defined patient groups with an active disease process, not outcomes that transfer to other populations, and the compound remains investigational.
Evidence & regulatory status
The phase 2b result, with its confidence intervals rather than its headline: placebo-corrected mean change in corneal nerve fiber area at day 28 was 109 micrometres squared (95% CI -429 to 647) at 1 mg, 697 (95% CI 159 to 1236, P = 0.012) at 4 mg, and 431 (95% CI -130 to 992) at 8 mg (PMID 28475703, n = 64). Two of the three intervals cross zero. The dose that separated from placebo was the middle one.
That non-monotonic pattern is the single most useful fact on this page, because it contradicts the assumption most peptide sources carry over from other compounds. Doubling the 4 mg dose did not double the effect; it produced a smaller point estimate with an interval that includes no effect at all. Any inference that a larger amount would do more is contradicted by the trial's own numbers.
The programme changed both route and frequency partway through, which means "the ARA-290 protocol" is not one thing. The 2012 pilot dosed 2 mg intravenously three times weekly (PMID 23168581); every later trial dosed subcutaneously once daily (PMID 24136731, 25387363, 28475703). Sources that quote a single canonical schedule are quoting one arm of one study.
Registry status, read rather than counted: four registered trials name cibinetide or ARA-290 as an intervention. NCT02039687 (Araim Pharmaceuticals) is completed at 64 participants and corresponds to the phase 2b; NCT02070783 (Leiden University Medical Center) is completed at 36 and studied cognitive and neural effects; NCT01933529 has 24 participants and a status listed as unknown; and NCT06626971 (Belfast Health and Social Care Trust), a phase 2 in diabetic macular oedema, is terminated with 9 enrolled. There is no registered phase 3.
Absence, stated as a finding: no human pharmacokinetic study of cibinetide is indexed in PubMed. The one study in healthy volunteers (PMID 26431906) measured emotional processing, not blood levels. The published literature is 75 records naming ARA-290 or cibinetide in title or abstract, concentrated in sarcoidosis, diabetic neuropathy and preclinical mechanism work.
Regulatory status: cibinetide, developed by Araim Pharmaceuticals, is investigational and not FDA-approved for any indication.
Research-use framing: material supplied as ARA-290 is for laboratory and research purposes only. The figures described here reflect published trial protocols, not clinical guidance, and no dose has been established for use outside a trial.
Research timeline
Dated milestones taken from the primary records: the molecule's discovery, its first registered human study, the trials that shaped the evidence and the regulatory decisions. Each entry links to the record it comes from.
A PNAS paper shows that helix B of erythropoietin, and an 11-amino-acid peptide modelled on its water-facing surface, protect tissue in rodent models of stroke and kidney ischaemia without stimulating red-cell production; that 11-residue peptide is the parent of ARA-290. PMID 18676614
The first randomized, double-blind trial enrols 22 patients with sarcoidosis and small-fibre neuropathy symptoms for four weeks of intravenous ARA-290 or placebo: the neuropathy screening score improves more than with placebo and no safety concern is raised. PMID 23168581
A placebo-controlled trial of 28 days of daily under-the-skin ARA-290 in sarcoidosis-associated small nerve fibre loss reports better neuropathic symptoms and a rise in small nerve fibre density in the cornea. PMID 24136731
A phase 2 study in type 2 diabetes with painful neuropathy, 28 days of daily ARA-290 or placebo followed by a month without treatment, reports better HbA1c and blood lipids over the 56 days and fewer neuropathic symptoms. PMID 25387363
A randomized, double-blind study gives one dose of ARA-290 or placebo to 36 healthy volunteers and tests emotional processing a week later: some measures shift, but mood does not change and the results do not clearly point to an antidepressant effect. PMID 26431906
A 28-day phase 2b trial in 64 patients with sarcoidosis-associated small nerve fibre loss and neuropathic pain, run under the name cibinetide, tests three doses against placebo: on the primary endpoint, corneal nerve fibre area, only the middle dose separates from placebo. PMID 28475703
A Belfast trial of ARA-290 in diabetic macular oedema ends as terminated after enrolling nine patients; the registry gives the reason as the study drug's expiry with no replacement available. ClinicalTrials.gov · NCT06626971
The British Journal of Pharmacology retracts a 2014 mouse study in which the same peptide, as pHBSP, had reduced diet-induced insulin resistance. PMID 38433016
Molecular Medicine retracts a 2012 rat study reporting that delayed pHBSP lessened acute kidney injury, the second animal paper on this peptide to be withdrawn. PMID 41749083
Records checked Oct 4, 2026
Claims at a glance
The claims most often made about this compound, each with the strongest kind of evidence we found for it. The grade says what was studied, not whether the claim is true; the line beside it says what that study showed.
Regrows damaged small nerve fibresHuman, randomised trial. In a 28-day randomised trial of 64 people with sarcoidosis nerve loss, corneal nerve fibre area rose against placebo in the middle dose group only, not the lowest or highest. PMID 28475703
Relieves neuropathic painHuman, randomised trial. In a randomised double-blind pilot of 22 sarcoidosis patients, a neuropathy symptom score improved against placebo, but pain intensity improved equally in both groups. PMID 23168581
Improves blood sugar control in type 2 diabetesHuman, non-randomised. One small 28-day placebo-controlled phase 2 study reported better HbA1c and blood lipids over 56 days; it has not been repeated. PMID 25387363
Lifts mood like an antidepressantHuman, randomised trial. In a randomised double-blind study of 36 healthy people, mood did not change and the emotional-processing results did not clearly point to an antidepressant effect. PMID 26431906
Treats diabetic eye diseaseNo study found. The one trial in diabetic macular oedema was stopped at nine participants because the study drug expired, and it has no results. NCT06626971
The reasoning behind each grade, study by study, is in this guide's Benefit & Outcome Review.
Grades checked Oct 6, 2026
A printable reference sheet with the compound's key facts, storage guidance and a vial record comes with All-Access Lifetime.
Half-life & pharmacokinetics
The figure this page previously published — a plasma half-life "on the order of minutes" — is withdrawn, because no human pharmacokinetic study of cibinetide is indexed in PubMed and the number traces to no measurement we can open. What the literature does state, and what actually answers the question behind it, is that the duration of biological effect is decoupled from plasma exposure: the mechanism review describing this molecule's development is titled around the long-lasting effects of a peptide that is not present for long, and attributes them to downstream innate-repair-receptor signaling and tissue repair rather than to a sustained blood level (PMID 25728128). That is why a short-lived peptide was given on a once-daily schedule in trials, and it means plasma half-life is the wrong number to reason with here even if one existed.
Reported side effects & toxicology
In the published phase 2b no significant safety issues were identified in any treatment group, and the compound was generally well tolerated across the 28-day period; the type 2 diabetes study likewise reported no potential safety issues over 56 days of observation. Injection-site reactions are the commonly reported issue. One point is structural rather than incidental: ARA-290 was designed not to stimulate erythropoiesis, so it is not expected to raise haemoglobin or haematocrit the way EPO does — that separation is the molecule's design rationale. Human safety data beyond short trial durations in specific patient groups are limited, and long-term safety has not been established. A phase 2 in diabetic macular oedema (NCT06626971, run 2016-2017) was terminated with 9 participants enrolled; the registry gives the reason as the study drug's expiry with no replacement available. These are reported observations, not an exhaustive safety profile.
Storage & handling
Lyophilized (unreconstituted) vials are typically stored refrigerated and protected from light; the sealed powder is generally described as stable at room temperature for short periods before use.
After reconstitution, keep refrigerated at about 2-8 C, protect from light, and use within a few weeks; do not freeze and avoid shaking.
As with any multi-dose vial reconstituted in bacteriostatic water, the in-use window follows the labeling if the vial states one and USP <797>'s 28-day cap after first entry if it does not — a point our bacteriostatic water pages set out in full.
References
Compiled from the primary records: PubChem CID 91810664 for identity; PubMed records 23168581 (22 patients, 2 mg intravenously three times weekly), 24136731 (28 days daily subcutaneous), 25387363 (type 2 diabetes, 4 mg daily) and 28475703 (phase 2b, 64 participants, corneal confocal microscopy endpoints with confidence intervals), plus the mechanism review 25728128; and ClinicalTrials.gov records NCT02039687, NCT02070783, NCT01933529 and NCT06626971. No phase 3 outcome data exist and the compound remains investigational. Provided for educational purposes only and not as medical advice.
Evidence File
The ARA-290 Evidence File: Four Names, No Search That Finds All of It, and Two Retractions Nobody Selling It Has Mentioned
ARA-290 has an unusually honest literature: small, mostly careful, and not inflated by synonym expansion the way most compounds in this library are. Its problem is the opposite one. The molecule answers to four different names, the name printed on the label finds well under two-thirds of its papers, and the fragments look reassuringly consistent because nobody is reading all of them at once. Assembled into one corpus it comes to 105 records, five of which carry a clinical-trial publication type — and two of which have been retracted, one in February of this year. This file names every record that matters and states what survives.
105 records in the corpus, once all four names are searched
The name on the label finds 59% of them
5 trial-typed records — the entire clinical literature
2 retracted papers, the second retracted in February 2026
One molecule, four names, and no search that finds all of it
The corpus by species, which is where the balance sits
The five trial-typed records, opened one at a time
Two retractions, and the second one is from February this year
The registry: four studies, and the newest one stopped because the drug ran out
The 28-day ceiling, and the things that have never been measured
6 more sections in the Evidence File for ARA-290
Unlock the Evidence File, Sourcing File and Benefit & Outcome Review for ARA-290 for $14 — or every compound in the library, plus the printable reference sheets, for $99.
The sections above this one stay free to read without an account.
Sourcing File
The ARA-290 Sourcing File: Two Database Records, 17 Daltons Apart, and Both of Them Are Called ARA-290
This compound's identity problem is not a counterfeit problem. There is no approved drug in its class to substitute, and no lucrative near-neighbour to pass off. The problem is that the molecule exists in two forms — one with a cyclised N-terminus and one without — which sit in two separate PubChem records under two separate InChIKeys, differ by 17.03 daltons, and are both routinely called ARA-290 in the literature and on labels. A second, quieter shift of 0.98 daltons sits at a sequence position this peptide happens to carry. This file gives both numbers, computed from the primary records, and the order in which to read a certificate.
2 PubChem records, 2 InChIKeys, 1 name in common use
17.027 Da between the two forms — 1.35% of the mass
0.984 Da is the second shift, at an Asn-Ser motif
Dosed in milligrams, not micrograms — the vial arithmetic changes
The identifier chain, re-derived from PubChem
The 17-dalton question: which of the two forms is in the vial
The 0.98-dalton question, which is the one a certificate will not catch
This compound is dosed in milligrams, and that changes the vial arithmetic
Reading a certificate for this compound, in order
5 more sections in the Sourcing File for ARA-290
Unlock the Evidence File, Sourcing File and Benefit & Outcome Review for ARA-290 for $14 — or every compound in the library, plus the printable reference sheets, for $99.
The sections above this one stay free to read without an account.
Benefit & Outcome Review
The ARA-290 Benefit & Outcome Review: One Real Signal in One Rare Disease, and a Dose Curve That Runs Backwards
The honest position on this compound is narrower than either its promoters or its critics allow. In sarcoidosis-associated small fibre neuropathy — a rare, poorly treated condition — three separate trials found something, and the largest measured nerve regrowth rather than asking patients how they felt. That is a real result and it deserves to be stated first. But the same trial's own confidence intervals show two of three doses failing to separate from placebo, with the highest dose performing worse than the middle one; the only study in healthy adults did not support the claim it was designed to test; and every other use this compound is sold for rests on rodents. This review takes each claim in turn.
697 µm² at 4 mg — the one dose that separated from placebo
2 of 3 confidence intervals cross zero
8 mg performed worse than 4 mg
36 healthy adults — the only study in people without a diagnosis
Claim one: it regrows nerve fibres — true in one disease, and here are the measurements
The dose curve runs backwards, and that matters more than the p-value
Claim two: it improves metabolic control
Claim three: it lifts mood — the one study in healthy people, and it did not find what it looked for
Claim four: it is well tolerated
The honest closing summary
6 more sections in the Benefit & Outcome Review for ARA-290
Unlock the Evidence File, Sourcing File and Benefit & Outcome Review for ARA-290 for $14 — or every compound in the library, plus the printable reference sheets, for $99.
Quick answers about guide scope, access, and educational use context.
What is ARA-290?
ARA-290, also called cibinetide or pHBSP, is an 11-amino-acid peptide derived from the helix B surface of erythropoietin — pyroGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser, PubChem CID 91810664, C51H84N16O21, 1257.3 g/mol, CAS 1208243-50-8. It selectively activates the innate repair receptor to produce anti-inflammatory and tissue-protective effects without stimulating red-blood-cell production the way EPO does. It is investigational, not FDA-approved, and supplied for research use only.
What dose of ARA-290 was used in trials?
It depends which trial. The phase 2b in painful sarcoid neuropathy tested 1, 4 and 8 mg by daily subcutaneous injection for 28 days (PMID 28475703); the type 2 diabetes study used 4 mg subcutaneously daily for 28 days (PMID 25387363); and the first sarcoidosis pilot used 2 mg intravenously three times weekly for four weeks (PMID 23168581). These are trial figures for educational context, not recommendations.
Is a higher ARA-290 dose more effective?
Not in the only trial that tested more than one. Placebo-corrected change in corneal nerve fiber area at day 28 was 109 (95% CI -429 to 647) at 1 mg, 697 (159 to 1236, P = 0.012) at 4 mg and 431 (-130 to 992) at 8 mg. The 8 mg interval crosses zero; the 4 mg one does not. Within that study the highest dose tested was not the one that demonstrated the effect.
What is ARA-290's half-life?
No human pharmacokinetic study of cibinetide is indexed in PubMed, so we no longer publish a figure — an earlier version of this page said "on the order of minutes" and that number traces to no measurement. The more useful published point is that the biological effect is decoupled from plasma exposure, attributed to innate-repair-receptor signaling and downstream repair rather than to a sustained blood level (PMID 25728128).
Does ARA-290 raise red blood cell count like EPO?
It is specifically designed not to. ARA-290 does not bind the classical homodimeric EPO receptor that drives erythropoiesis; it targets the innate repair receptor instead. Separating tissue protection from haematopoietic stimulation — and therefore from EPO's thrombotic risk — is the entire rationale for the molecule, and the trials reported no significant safety issues in this respect.
Has ARA-290 been studied in healthy people?
In one published study. A randomized, double-blind study at Leiden gave a single dose of ARA-290 or placebo to 36 healthy volunteers and tested how they processed emotional faces and words a week later: some measures shifted, mood did not, and the authors concluded the results do not clearly support an antidepressant-like profile (PMID 26431906, 2015; registered as NCT02070783). Every other published human dose comes from a patient group with an active disease process — sarcoidosis with small fiber neuropathy, or type 2 diabetes with painful neuropathy. That matters mechanistically, because the receptor the molecule targets is described as induced by injury and inflammation rather than present in normal tissue.
How far has ARA-290 got in development?
Phase 2. Four registered trials name it as an intervention: the Araim phase 2b completed at 64 participants (NCT02039687), a Leiden study in healthy volunteers completed at 36 (NCT02070783), a 24-participant study whose status is listed as unknown (NCT01933529), and a phase 2 in diabetic macular oedema terminated with 9 enrolled (NCT06626971). No phase 3 is registered and no outcome data beyond phase 2 exist.
Does this page tell me how much ARA-290 to use?
No. The amounts shown describe published clinical trial protocols, provided for educational context. This page does not recommend a personal dose, route or frequency and is not medical advice. ARA-290 is investigational: it has no approved label, and no dose has been established outside a trial.
Compliance and trust notes
Educational content only; no personalized health or outcome claims.
No personalized use recommendation outputs.
Use this material for general learning and research-context literacy.
A certificate of analysis (COA) is a laboratory’s report on one sample of one batch. The single most useful thing to know about it is that purity and identity are two separate results that fail in different ways. A high purity figure says the sample was mostly one substance; it does not say that substance was ARA-290. Identity — normally a mass-spectrometry result matching the expected molecular weight — is what establishes what the material actually is, and a certificate reporting purity alone has not answered that question.
Two further limits are worth holding onto. Mass per vial is its own test: a vial can be 99% pure and still contain less material than the label claims. And sterility, endotoxin, heavy metals and residual solvent screening are separately commissioned tests, usually priced individually — so a “third-party tested” badge asserts none of them unless the certificate names them. Check that the batch or lot number on the document matches the vial in front of you; an unmatched certificate describes someone else’s material.
Medibact does not test, endorse or resell peptides, and publishes no rating of any laboratory. How to read a peptide certificate of analysis walks through the document section by section, and what each COA field establishes covers the field-by-field detail and the laboratories that publish their methods.
You’ll need bacteriostatic water
The diluent for reconstituting ARA-290
Reconstitution is volume arithmetic — it assumes a lyophilized vial is dissolved in bacteriostatic water, which is sterile water preserved with 0.9% benzyl alcohol. The preservative is what allows a vial to be entered more than once; plain sterile water carries none and is single-entry by design. Medibact supplies USP-grade Bacteriostatic Water for Injection in a 30 mL multi-dose vial, produced in an FDA-registered U.S. facility and shipped from the United States, for research use only. One 30 mL vial covers 30 reconstitutions at 1 mL each, 15 at 2 mL, or 10 at 3 mL — division only, not a dosing recommendation.
Educational use only — not medical advice. This guide summarizes information reported in published research and community practice for educational purposes. It is not medical advice and not a recommendation to use any compound. Any doses, schedules, or combinations shown are examples of what has been reported, not instructions for you. Many peptides described here are research compounds that are not FDA-approved for the uses discussed and may be investigational or restricted. Effects, risks, and legal status vary; individual needs and results vary. Consult a qualified, licensed healthcare professional before making any decision. Do not use this content to diagnose, treat, or dose yourself.
