RecoveryCibinetidepHBSP

ARA-290 (Cibinetide)

Q: How is ARA-290 different from EPO?

EPO raises red-blood-cell production (and, when misused, blood doping risk). ARA-290 is copied from EPO's tissue-protective region and selectively activates a different receptor (the EPOR/CD131 'innate repair receptor') that's switched on in injured tissue. In trials it did not raise the red-cell count — that non-erythropoietic profile is its defining feature.

Q: Does it actually relieve neuropathic pain?

The evidence is mixed. Objective nerve measures (like corneal and skin nerve-fibre density) improved in the sarcoidosis and diabetes trials, but the patient-reported pain endpoints often did not clearly beat placebo — for example, pain reduction missed significance in the effective 4 mg arm of the dose-finding study. Promising surrogate signals, unproven symptom benefit.

Q: Is ARA-290 approved or proven?

No. It reached small Phase 2/2b trials, earned FDA orphan-drug and fast-track designations (which reward rare-disease intent, not proven efficacy), but never completed a Phase 3 trial and is not approved anywhere. There was no active development program that could be confirmed.

Q: What dose did the trials use?

Most often 4 mg subcutaneously once daily for 28 days. Notably, that 4 mg dose worked better than the higher 8 mg dose — a non-dose-proportional response. There is no validated dose for general use, and these figures are trial doses cited for reference, not a protocol.

Q: Is ARA-290 banned in sport?

It is not named on the 2026 WADA Prohibited List, but ARA-290 is by definition an 'innate repair receptor agonist' — the exact class WADA names under S2.1.5 (giving asialo-EPO and carbamylated EPO as examples). On that basis it is very likely captured by class even though it isn't listed by name, so it should be treated as prohibited. Athletes must verify against the official WADA list and their anti-doping authority.

EPO-derived 11-mer · innate repair receptor agonist · tissue-protective, non-erythropoietic

ARA-290 (cibinetide) is one of the more biologically interesting peptides in this library, and also one where the human proof is genuinely thin. It is a short eleven-amino-acid peptide built from the surface of erythropoietin's 'helix B' — the region of the EPO molecule that drives tissue protection rather than red-blood-cell production. The clever idea is that ARA-290 selectively activates a different receptor (the 'innate repair receptor,' a pairing of the EPO receptor with the CD131 co-receptor) that is switched on in injured and inflamed tissue, so it can be anti-inflammatory and help small nerve fibres regenerate without raising the blood count or the clotting risk that limit EPO itself. The catch is the evidence: the human data are a handful of small, short Phase 2 trials (roughly 22 to 64 participants, dosing for about a month) from a few overlapping research groups, in conditions like sarcoidosis-related small-fibre neuropathy and diabetic neuropathy. The picture is mixed — objective markers of nerve regeneration improved, but the actual pain endpoints often failed to beat placebo, and the effective dose was 4 mg rather than the higher 8 mg (a non-typical, non-dose-proportional response). It has earned orphan-drug and fast-track designations but has never completed a Phase 3 trial, is not approved anywhere, and has no active development that could be confirmed. The fair framing: a mechanistically novel, short-term-safe peptide with promising surrogate signals — not a proven therapy.

The short version

Erythropoietin (EPO) is the body's red-blood-cell hormone, but scientists noticed it also protects injured tissue — and that the two jobs use different parts of the molecule. ARA-290 is a small peptide copied from the 'tissue-protective' face of EPO (its helix B). The goal was to keep the protective, anti-inflammatory effect while throwing away the blood-building effect, because raising the blood count (what EPO does, and why it's abused in sport) brings clotting and cardiovascular risk.

It works by hitting a specific receptor that the body assembles on damaged tissue — a partnership between the EPO receptor and a co-receptor called CD131, nicknamed the 'innate repair receptor.' Because that receptor mostly appears where there's injury or inflammation, the idea is that ARA-290 acts where it's needed and leaves healthy tissue and the bone marrow alone. In trials it did not raise red-cell counts, which is the key safety distinction from EPO.

The honest limitation is the strength of the human evidence. The trials are small (tens of patients), short (about a month of dosing), and come from a few closely related research groups, mostly in nerve conditions such as the small-fibre neuropathy seen in sarcoidosis and in diabetes. They showed improvements in objective nerve measurements (like the density of tiny nerve fibres in the cornea and skin) — but the pain scores, which matter most to patients, frequently did not clearly beat placebo. Oddly, the middle dose (4 mg) worked better than the higher dose (8 mg). ARA-290 has never finished a large confirmatory trial, isn't approved for anything, and there's no active program we could confirm. So it's a promising, distinctive idea with encouraging early signals — not an established treatment.

Molecular identity

Specs

Molecular formula: C₅₁H₈₄N₁₆O₂₁
Molecular weight: 1257.3 g/mol (average)
Monoisotopic mass: 1256.5997 Da
CAS / UNII: 1208243-50-8 · 9W5677JKDA
PubChem CID: 91810664

Sequence: Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (pyroGlu-EQLERALNSS)PubChem CID 91810664 (N-terminal pyroglutamate)
Class: Linear 11-amino-acid peptide; EPO helix-B-derivedPubChem CID 91810664; innate-repair-receptor literature
Receptor / mechanism: Innate repair receptor — EPOR/CD131 (β-common) heteromer; non-erythropoieticBrines/Cerami innate-repair literature; trial introductions
Half-life: ~20 min terminal (human plasma, 4 mg SC) — very short; tissue-protective effect outlasts plasma levelsPMID 25387363Half-life curve →
Regulatory status: Not approved anywhere; FDA orphan + fast-track designations only; reached Phase 2/2b, no Phase 3FDA designation releases; no NDA/BLA on record

Plain English

Mechanism

Erythropoietin signals through two different receptor arrangements. The classic red-cell-producing signal goes through a receptor built of two EPO-receptor units (the EPOR homodimer). The tissue-protective signal goes through a different complex: one EPO receptor paired with the β-common receptor, CD131 — together called the 'innate repair receptor.' ARA-290 is engineered to selectively activate this innate repair receptor and not the red-cell-producing homodimer.

That selectivity is the whole point. Because ARA-290 doesn't effectively engage the EPOR homodimer, it does not stimulate erythropoiesis — in human trials it raised neither the red-cell count nor the associated clotting/cardiovascular risk that limit EPO. And because the innate repair receptor is upregulated on injured and inflamed tissue, the peptide's activity is biased toward damaged areas: activating it there suppresses pro-inflammatory signaling and apoptosis and supports regeneration of small nerve fibres. This is the mechanistic basis for the corneal and intra-epidermal nerve-fibre regrowth (including GAP-43-positive regenerating fibres) reported in the sarcoidosis trials.

It's worth being precise about what's established and what isn't. The non-erythropoietic, tissue-targeted signaling is well-motivated and consistent with the trial safety data. The downstream clinical benefit — actually relieving neuropathic pain or changing disease course — is where the evidence thins out, with surrogate nerve-regeneration markers outperforming the symptom endpoints that matter to patients.

Sources:PMID 25387363 PMID 28475703

Why people reach for it

Potential benefits

ARA-290 is one of the more mechanistically distinctive peptides here — EPO's tissue-protective effect without the blood-building risk. Here's what draws people to it, with the honest caveat that the human evidence is small, short, and mixed.

EPO's repair side without the blood-building risk — ARA-290 is copied from erythropoietin's tissue-protective helix B and selectively activates the 'innate repair receptor' — so in trials it did not raise red-cell counts or the clotting risk that limits EPO, which is its defining appeal.
A signal aimed at injured, inflamed tissue — Because that innate repair receptor appears mainly where there's injury or inflammation, the peptide's anti-inflammatory, pro-repair activity is biased toward damaged areas rather than healthy tissue.
Reached for on small-fibre nerve regeneration — In the sarcoidosis and diabetes trials, objective nerve markers improved — corneal nerve-fibre area and GAP-43-positive regenerating fibres at the 4 mg dose — which is why it's reached for on neuropathy and nerve-injury goals.
A favorable short-term tolerability profile — Across the Phase 2 trials it was generally well tolerated over the ~28-day dosing windows with no major safety signal — though total human exposure remains small and short.

Sources:PMID 28475703 PMID 25387363 PMID 24136731

What people reach for ARA-290 for, drawn from what the research reports and how it's used — not proven outcomes or medical claims. Honest limits: the human data are a few small, short Phase 2 trials, the pain endpoints often failed to beat placebo, and there is no Phase 3 or approval.

Implied timing

Best time to dose

Implied best time

Anytime (consistent)

Most people take ARA-290 at a consistent daily time — its tissue-protective signaling isn't tied to a specific hour, so regularity matters more than the exact time, with at most an optional evening lean.

ARA-290 works by activating the innate repair receptor on damaged tissue to suppress inflammation and drive nerve-fibre regrowth — a repair process that unfolds over days, not within a single dosing window, so no time of day is mechanistically required.
Its plasma half-life is very short (~20 minutes), but the tissue-protective effect outlasts plasma levels — so the dose isn't something you schedule around, and a consistent daily time is the practical lever the trials' once-daily cadence supports.
Some users put the dose in the evening to line the repair signal up with the body's overnight recovery window — a reasonable habit by analogy to other repair peptides, but reasoned, not something ARA-290's trials tested.

No study establishes an ideal time of day for ARA-290 — this is reasoned from its mechanism and how it's used. As a rule of thumb most peptide dosing lands in the midday-to-evening window; for ARA-290 any consistent time works, with an optional (unproven) evening lean for those aligning it with overnight repair.

Sources:PMID 25387363

How to run it

Dosing & protocol

ARA-290 is dosed here as a subcutaneous injection — the form sold as a research peptide and the route the on-page calculator is built for. The only human dose with primary-source grounding is 4 mg SC once daily for 28 days, drawn from the Phase 2 trials. That figure is used as the anchor throughout; the ranges and schedule below are community convention extrapolated from that anchor and ARA-290's biology.

Thin human proof — foregrounded, not buried: ARA-290 has only small, short Phase 2 trials; pain endpoints often missed significance; the dose response is non-monotonic (4 mg outperformed 8 mg); no Phase 3, no approval. Every practical number here is convention anchored to the trial dose, not a validated regimen.

Tiered dose ranges

The trial data anchor is narrow — 4 mg SC daily — and the non-monotonic finding means escalation is not supported by evidence.

Trial-anchored (primary reference):: 4 mg subcutaneously once daily — the effective arm in both the sarcoidosis dose-finding trial (Culver 2017) and the diabetic-neuropathy study (Brines 2015). This is the only dose with positive objective findings; 8 mg did not outperform it.
Low / exploratory:: 2–3 mg SC daily — used by some practitioners as a cautious entry point, staying below the trial dose while preserving the mechanism.
Do not escalate above 4 mg:: The Phase 2b dose-finding study found 8 mg inferior to 4 mg on the primary nerve-fibre endpoint. The non-monotonic response is a documented feature of this compound; higher is not better here.

Subcutaneous administration

ARA-290 is injected into subcutaneous fat; site, rotation, and timing are the actionable choices.

Injection site:: The abdomen (a couple of inches clear of the navel), the outer thigh, or the love-handle area. Rotate sites between doses so no single spot is used repeatedly — prevents local irritation and lipohypertrophy.
Measuring the dose:: On a U-100 insulin syringe from the reconstituted vial. At the standard mix (10 mg / 2 mL = 5,000 mcg/mL): 1,000 mcg = 20 IU · 2,000 mcg = 40 IU · 4,000 mcg (trial reference dose) = 80 IU. The calculator converts for any vial size.
Time of day:: The trials did not specify a time window, and ARA-290 isn't time-locked — consistent timing each day matters more than the specific hour. Some users lean evening to align with the overnight repair window (reasoned, not proven). See Best time to dose above.
Food window:: Subcutaneous dosing does not compete with food for absorption; the injection can be given independent of meals.

Cycle & washout

The trial duration was 28 days — that is the only schedule with any human data; anything beyond it is extrapolation.

Trial-matched cycle:: 28 days (4 weeks) of daily subcutaneous dosing, matching the Phase 2 protocol. The nerve-regeneration markers that moved (corneal nerve-fibre area, GAP-43+ regenerating fibres) were measured at day 28.
Extended course (community convention):: Some practitioners run 6–8-week courses before reassessing, reasoning that small-fibre regeneration is slow (weeks to months). This goes beyond the trial evidence; framed honestly as a plausible extrapolation.
Washout:: Follow with a 4-week break. Re-check any neuropathy symptom scores or, if accessible, corneal confocal microscopy readings during the off period to gauge whether the benefit persisted.

Reconstitution at a glance

The on-page calculator does this live; the quick reference for a 10 mg vial:

Mixing:: 10 mg vial + 2 mL bacteriostatic water = 5,000 mcg per mL. On a 100-unit (1 mL) insulin syringe: 1,000 mcg = 20 IU · 2,000 mcg = 40 IU · 4,000 mcg (trial reference dose) = 80 IU.
Why 2 mL:: Keeps the concentration practical for the small volumes involved. If drawing very small doses, adding up to 5 mL water creates more syringe-unit spread and reduces measurement error — the calculator adjusts automatically.

Sources:PMID 28475703 PMID 25387363 PMID 24136731

Substrate the signal needs

Nutritional cofactor precision

ARA-290's two documented jobs — suppressing neuroinflammation and stimulating small-fibre regrowth — define the cofactor strategy. Three questions structure the cards: what SUPPLIES the raw material nerve fibres rebuild from, what MITIGATES the oxidative stress that damages them, and what AMPLIFIES the repair signal by removing the environmental block.

Reasoned from ARA-290's innate-repair-receptor mechanism plus established nerve-health nutrition — not an ARA-290 cofactor study. Supplement doses are common clinical ranges; none is ARA-290-specific.

SUPPLY nerve substrate — B-vitamins + acetyl-L-carnitine

Regrowing small nerve fibres consumes B-vitamin cofactors and carnitine; a deficiency in any of these independently causes neuropathy.

Methylcobalamin B12:: 1,000 mcg (1 mg) daily — the active, neurally available form of B12. Peripheral-nerve maintenance; deficiency is a direct cause of small-fibre neuropathy. Methylcobalamin preferred over cyanocobalamin for nerve applications.
Pyridoxal-5'-phosphate (B6) + methylfolate:: B6 as P5P 50 mg + methylfolate 400–800 mcg daily — B6 is a rate-limiting cofactor in myelin synthesis; folate drives homocysteine clearance (elevated homocysteine damages nerve vessels). Avoid high-dose plain pyridoxine (>100 mg), which paradoxically causes neuropathy.
Acetyl-L-carnitine (ALCAR):: 1–2 g daily — supports mitochondrial function in Schwann cells and provides substrate for nerve-membrane repair. A Cochrane review found ALCAR reduced neuropathic pain in diabetic neuropathy trials; complements ARA-290's regeneration signal with a direct substrate supply.

MITIGATE oxidative nerve stress — alpha-lipoic acid + DHA

Oxidative damage to nerve membranes and myelin is the mechanism through which metabolic and inflammatory injury stalls regeneration; these two nutrients directly target it.

Alpha-lipoic acid (ALA):: 600 mg once daily — the best-evidenced nutraceutical for diabetic peripheral neuropathy, with multiple controlled trials; reduces oxidative damage to nerve tissue and improves nerve conduction. Synergistic with ARA-290's nerve-fibre-regeneration signal: ALA makes the environment less hostile while ARA-290 drives regrowth.
Omega-3 DHA:: 1–2 g DHA daily (via fish oil or algae oil) — DHA is the dominant structural fatty acid in nerve membranes and myelin; adequate DHA reduces neuroinflammation and is incorporated directly into regenerating fibre membranes. EPA adds anti-inflammatory support at the vascular supply to peripheral nerves.

AMPLIFY — tight glucose control (metabolic context)

If ARA-290 is being used in a metabolic-neuropathy context, blood-sugar control is not optional — a persistently hostile glucose environment blunts nerve repair regardless of the peptide signal.

Why this matters for ARA-290:: The ARA-290 diabetes trial (Brines 2015) showed HbA1c fell alongside nerve improvements — consistent with the established fact that high blood sugar is itself the primary driver of small-fibre damage. Regenerated fibres are re-injured by sustained hyperglycemia; the peptide cannot outrun a hostile metabolic environment.
Practical steps:: Dietary: lower-glycemic carbohydrates, adequate fiber, limit refined sugar. Nutritional support: magnesium glycinate 300–400 mg (improves insulin sensitivity; deficiency is near-universal in metabolic disease) + chromium picolinate 200 mcg (glucose disposal). The goal is HbA1c below 7% if relevant; lower is better for nerve repair.

Combinations + timing

Stacking notes + timing windows

ARA-290's lever is narrow and specific: it activates the innate repair receptor on damaged tissue, suppressing local inflammation and driving small-fibre nerve regeneration. The best pairings come at the same injury from a different angle — structural rebuilding, cell migration — not the same receptor or the same anti-inflammatory pathway.

Mechanism-reasoned combinations — not regimens studied head-to-head. ARA-290's own human evidence is small and short, so any stack is doubly unproven. Doses are community convention; "reached for on" describes user goals, not proven indications. ARA-290 is very likely WADA-prohibited by class (S2.1.5) — athletes must verify.

ARA-290 + BPC-157

ARA-290 drives nerve-fibre regeneration through the innate repair receptor; BPC-157 drives tissue healing and angiogenesis through a complementary pathway.

Why it works:: BPC-157 has its own rodent literature for nerve and tendon repair, and it promotes new blood-vessel growth (angiogenesis) — the vascular supply that regenerating nerve fibres depend on. ARA-290 clears the inflammatory block and activates the nerve-repair receptor; BPC-157 builds the structural and vascular scaffold the fibre grows into. Two different levers, not one lever twice.
The protocol:: ARA-290 4 mg SC once daily (trial-anchored dose) + BPC-157 250–500 mcg SC once daily. Can be co-injected or as two nearby sites, rotated across the abdominal area.
Outcome:: The combination users reach for on neuropathy, nerve-injury, and tissue-inflammation goals — particularly where nerve regeneration and vascular support are both wanted.

ARA-290 + BPC-157 + TB-500

The three-lever nerve-and-soft-tissue recovery trio: nerve-repair signal + structural/vascular scaffold + cell-migration signal.

Why it works:: TB-500 (Thymosin β4) promotes the migration of repair cells — endothelial and satellite cells — into injured tissue; BPC-157 rebuilds the structural and vascular scaffold; ARA-290 activates the innate repair receptor at the injury site and suppresses the neuroinflammation that would otherwise slow regrowth. Three distinct jobs, three different mechanisms.
The protocol:: ARA-290 4 mg SC daily + BPC-157 250–500 mcg SC daily + TB-500 on its own schedule: typically 5–10 mg/week in a loading phase for 4–6 weeks, then 2–5 mg/week maintenance. TB-500 is often run at lower frequency (2–3×/week) rather than daily.
Outcome:: Reached for on broader nerve-and-soft-tissue injuries where all three components of repair — inflammation control, structural healing, and cell recruitment — are wanted simultaneously.

Reconstitution math

Reconstitution calculator

Calculated for a 1 mL U-100 insulin syringe (100 units/mL).

Peptide per vial

BAC water added

Desired dose

Units per dose

Draw to this mark on a U-100 syringe

Volume per dose: 0.2 mL
Doses per vial: 10
Concentration: 5 mg/mL

One vial lasts

Daily: 10 days
Every other day: 20 days
5×/week: 14 days

Research use only. Not for human consumption. Outputs are reference values based on research literature — verify all measurements independently.

From the studies

Side effects from research

The headline safety point is favorable and is the whole rationale for the molecule: across the Phase 2 trials, ARA-290 did not stimulate erythropoiesis — it did not raise the red-cell count or hematocrit — so it avoids the thrombotic and cardiovascular risks that limit EPO itself. The trials reported it as generally well tolerated over their roughly four-week dosing windows, with no major safety signal identified.

That reassurance comes with real limits. The total human exposure is small (tens of patients per trial) and short (about a month), so rare or long-term effects would not have been detected. Subcutaneous dosing carries the usual local injection-site considerations. There is no modern large-scale or long-term safety surveillance.

Gray-market sourcing adds purity and identity risk independent of the peptide. The honest summary is that ARA-290's short-term safety looks good — notably its non-erythropoietic profile — but its long-term safety is simply uncharacterized.

Sources:PMID 25387363

As reported in literature

Research dosing ranges

These are doses from small Phase 2 trials, shown for reference only — there is no validated or approved regimen. Read the table for the recurring split: objective nerve-fibre measures improved, while patient-reported pain endpoints often did not clearly beat placebo. Note too that the 4 mg dose, not the higher 8 mg, was the effective one.

Dose	Route	Model	Outcome	Sources:
2 mg	IV (3×/week)	Human pilot RCT — sarcoidosis small-fibre neuropathy (Heij 2012, N=22)	Neuropathy symptom score (SFNSL) improved vs placebo (p<0.05) and SF-36 pain/function improved — but the Brief Pain Inventory improved equally in both arms (a pain-endpoint null)	PMID 23168581
Daily ×28 d	SC	Human RCT — sarcoidosis small-fibre neuropathy (Dahan 2013)	Improved neuropathic symptoms, increased corneal nerve-fibre density, higher cold/hot pain thresholds (p=0.027 / p=0.032), longer 6-minute walk; benefit favored ARA-290	PMID 24136731
1 / 4 / 8 mg daily ×28 d	SC	Human Phase 2b dose-finding — sarcoidosis (Culver 2017, N=64)	Only the 4 mg arm improved corneal nerve-fibre area (+697 µm², p=0.012) and regenerating GAP-43+ fibres (p=0.035); 1 mg and 8 mg were not significant, and 4 mg pain reduction missed (p=0.157)	PMID 28475703
4 mg daily ×28 d	SC	Human Phase 2 — type 2 diabetes neuropathy/metabolic (Brines 2015)	HbA1c fell from baseline and stayed lower (p=0.002); neuropathic pain (PainDetect) fell ~18% at day 28 / ~23% at day 56 (p≈0.03); HDL up, triglycerides down; no safety signal	PMID 25387363

Quick answers

Frequently asked

How is ARA-290 different from EPO?

EPO raises red-blood-cell production (and, when misused, blood doping risk). ARA-290 is copied from EPO's tissue-protective region and selectively activates a different receptor (the EPOR/CD131 'innate repair receptor') that's switched on in injured tissue. In trials it did not raise the red-cell count — that non-erythropoietic profile is its defining feature.

Does it actually relieve neuropathic pain?

The evidence is mixed. Objective nerve measures (like corneal and skin nerve-fibre density) improved in the sarcoidosis and diabetes trials, but the patient-reported pain endpoints often did not clearly beat placebo — for example, pain reduction missed significance in the effective 4 mg arm of the dose-finding study. Promising surrogate signals, unproven symptom benefit.

Is ARA-290 approved or proven?

No. It reached small Phase 2/2b trials, earned FDA orphan-drug and fast-track designations (which reward rare-disease intent, not proven efficacy), but never completed a Phase 3 trial and is not approved anywhere. There was no active development program that could be confirmed.

What dose did the trials use?

Most often 4 mg subcutaneously once daily for 28 days. Notably, that 4 mg dose worked better than the higher 8 mg dose — a non-dose-proportional response. There is no validated dose for general use, and these figures are trial doses cited for reference, not a protocol.

Is ARA-290 banned in sport?

It is not named on the 2026 WADA Prohibited List, but ARA-290 is by definition an 'innate repair receptor agonist' — the exact class WADA names under S2.1.5 (giving asialo-EPO and carbamylated EPO as examples). On that basis it is very likely captured by class even though it isn't listed by name, so it should be treated as prohibited. Athletes must verify against the official WADA list and their anti-doping authority.

Primary sources

References

PMID 23168581Heij et al., Molecular Medicine 2012 — ARA-290 in sarcoidosis small-fibre neuropathy (pilot RCT, N=22)
PMID 24136731Dahan et al., Molecular Medicine 2013 — ARA-290 RCT in sarcoidosis neuropathy; corneal nerve-fibre density
PMID 28475703Culver et al., Invest Ophthalmol Vis Sci 2017 — Phase 2b dose-finding (NCT02039687); 4 mg effective, non-monotonic
PMID 25387363Brines et al., Molecular Medicine 2015 — ARA-290 4 mg SC ×28 d in type 2 diabetes neuropathy/metabolic (NTR3858)
PubChem CID 91810664PubChem record — identity (CID, formula, MW, CAS, sequence)
WADA 2026, S2.1.5WADA 2026 Prohibited List — S2.1.5 innate repair receptor agonists (ARA-290 captured by class, not named)

Research use only · Not medical advice · Updated 2026-06-01