Cibinetide

How does Cibinetide work?

Cibinetide (ARA-290) is an 11-amino-acid peptide derived from the helix-B domain of erythropoietin (EPO). It activates the innate repair receptor (IRR) — a heterocomplex of the EPO receptor and the β-common receptor (CD131) — driving anti-inflammatory, anti-apoptotic, and tissue-repair signaling. Crucially, it does NOT engage the EPOR homodimer that drives red-blood-cell production, so unlike EPO it does not raise hematocrit or carry EPO's thrombotic and hypertensive erythropoietic risks.

1. Helix-B origin [1]. Cibinetide is engineered from the helix-B region of erythropoietin. Brines and colleagues delimited EPO's tissue-protective activity to short helix-B-derived peptides that retain protective signaling while shedding erythropoietic activity.
2. Innate repair receptor (IRR) agonism [1]. It binds the innate repair receptor — a heterocomplex of the EPO receptor and the β-common receptor (CD131). This receptor is expressed on injured and inflamed tissue and mediates EPO's tissue-protective, rather than red-cell-stimulating, effects.
3. Anti-inflammatory and anti-apoptotic signaling [1][2]. IRR activation drives anti-inflammatory and anti-apoptotic pathways associated with tissue protection and repair, including in peripheral nerve tissue in the human trials.
4. Non-erythropoietic by design [1]. Because it does not engage the EPOR homodimer responsible for erythropoiesis, cibinetide does not raise hematocrit and lacks the thrombotic and hypertensive risks that accompany EPO's red-cell-stimulating activity. This is the central pharmacological distinction from EPO.
5. Nerve-fiber effects in humans [2][4]. In Phase 2 and Phase 2b trials, cibinetide was associated with increased corneal and skin nerve-fiber abundance — a surrogate marker consistent with small-fiber nerve regeneration.

What is Cibinetide used for?

Unlike most research peptides, cibinetide has real human Phase 2 randomized controlled trial data. It was investigated for sarcoidosis-associated small-fiber neuropathy and type 2 diabetic neuropathy, with a Phase 2b dose-ranging study confirming nerve-fiber effects at 4 mg/day. Endpoints were largely surrogate nerve-fiber biomarkers, the trials were small (N≈36 and 64) and short (28 days), and there is no Phase 3 confirmation.

1. Sarcoidosis small-fiber neuropathy — Phase 2 RCT [2]. Sarcoidosis patients with small-fiber neuropathy given 28 days of daily subcutaneous ARA-290 (4 mg) versus placebo showed improved neuropathic symptoms and increased corneal nerve fiber density (Dahan 2013).
2. Type 2 diabetes — Phase 2 RCT [3]. Type 2 diabetes patients self-injecting 4 mg/day subcutaneous ARA-290 for 28 days showed improved HbA1c and lipid measures and reduced neuropathic symptoms versus placebo (Brines 2014/2015).
3. Phase 2b dose-ranging [4]. A dose-ranging RCT (1/4/8 mg/day subcutaneous, 28 days, N=64) found that the 4 mg dose significantly increased corneal and skin nerve-fiber abundance, with pain reduction in those with moderate-to-severe baseline pain (Culver 2017).
4. Preclinical mechanism [1]. Brines and Cerami's 2008 PNAS work established the non-erythropoietic, tissue-protective mechanism of the helix-B-derived peptides that cibinetide belongs to.
5. Evidence caveats. Endpoints were largely surrogate nerve-fiber biomarkers rather than long-term clinical outcomes; trials were small and short (28 days); and no Phase 3 trial has confirmed these findings.

How long does Cibinetide take to work?

The human trials measured outcomes over a fixed 28-day course of daily subcutaneous dosing. Nerve-fiber and symptom changes were assessed at the end of that 28-day window; the trials were not designed to characterize onset within days, and there is no reliable durability data beyond the short trial periods.

In the Phase 2 and Phase 2b trials, cibinetide was given as 4 mg/day subcutaneously for 28 days, with neuropathic-symptom and nerve-fiber outcomes measured at the end of that period. Because these were short fixed-duration studies, there is no well-characterized day-by-day onset curve, and durability beyond a few weeks was not established. Effects reported (reduced neuropathic symptoms, increased corneal and skin nerve-fiber abundance) reflect the 28-day trial endpoint rather than a validated long-term trajectory. All of this is investigational — cibinetide is not an approved human therapy.

How is Cibinetide dosed?

Cibinetide is the rare research peptide with real trial dosing to report. The studied regimen was 4 mg per day subcutaneously for 28 days; the Phase 2b dose-ranging study compared 1, 4, and 8 mg/day, and 4 mg was the effective dose on nerve endpoints. This is presented as the investigational trial dose — not an approved, endorsed, or recommended human protocol.

How is Cibinetide administered?

In the human trials, cibinetide was given as a once-daily subcutaneous injection — under the skin, not into muscle — using a small insulin syringe. The trials did not specify food timing. For the practical mechanics of insulin syringes, units vs mg conversion, and subcutaneous technique, see the syringes and injection technique guide. Note that cibinetide is investigational and this reflects trial procedure, not an approved human protocol.

What does Cibinetide stack well with?

There are no studied cibinetide combinations. It is a non-erythropoietic, tissue-protective and anti-inflammatory peptide, conceptually adjacent to recovery peptides, but no controlled trial has tested it in any stack. The peptides below are listed only for orientation within the tissue-repair space — there is no controlled evidence of synergy with cibinetide, and none should be inferred.

1. No studied combinations. Every human cibinetide trial used it as a single agent. Any stack is speculative and unsupported by controlled data.
2. Recovery-peptide neighbors. Compounds like BPC-157 and TB-500 occupy the same broad tissue-repair category, but no study has combined them with cibinetide.
3. Other tissue-protective peptides. GHK-Cu, SS-31, and Thymosin Alpha-1 are mechanistically distinct; listing them here is for orientation only, not a recommendation to combine.
4. Do not invent synergy. Because cibinetide's only human data comes from single-agent Phase 2 trials, any additive or synergistic benefit with these peptides is unproven.

What are the side effects of Cibinetide?

In the Phase 2 and Phase 2b trials, cibinetide was generally well tolerated over the 28-day dosing period, with mild injection-site reactions the most commonly noted effect. Because it is non-erythropoietic, it does NOT raise hematocrit — a key safety contrast with EPO. The important limitation is duration: safety beyond a few weeks has not been established, and the trial populations were small.

Does Cibinetide interact with other drugs?

No significant drug-drug interaction data for cibinetide has been published. The trials did not report clinically meaningful interactions, but they were small and short, so any interaction profile should be considered unknown rather than established.

1. No published drug-drug interaction studies. There is no dedicated interaction data for cibinetide in the peer-reviewed literature.
2. Interactions are theoretical only. Any concern about combining cibinetide with other agents is speculative given the absence of controlled interaction data.
3. Small, short trials. The Phase 2 studies were not designed or powered to detect drug-drug interactions.

How should Cibinetide be stored?

1. Lyophilized (powder) form: Store at -20°C for long-term storage; refrigerate at 2–8°C for short-term.
2. Reconstituted solution: Store at 2–8°C; use within 28–30 days.
3. Reconstitute with bacteriostatic water for injection (BAC water). Swirl gently — do not shake.
4. Never freeze reconstituted solution.
5. Protect from light. Store in original carton.
6. Discard if cloudy, discolored, or contains particles.

What are the limitations of Cibinetide research?

Cibinetide has more human data than most research peptides — but the evidence is still early and narrow. It is not approved anywhere; the controlled trials were small (N≈36 and 64) and short (28 days); several primary endpoints were surrogate nerve-fiber biomarkers rather than long-term clinical outcomes; there is no Phase 3; and durability beyond a few weeks is unestablished.

Where to source Cibinetide

Cibinetide (ARA-290) is not FDA-approved for any human use and is sold only as a research-grade peptide. In PP's vetted vendor directory it is currently listed by Swiss Chems. Vendors highlighted here have been evaluated for transparent third-party testing, traceable batch documentation, and verified discount codes.

Cibinetide FAQ

References

1. Brines M, Patel NSA, Villa P, et al. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci U S A. 2008;105(31):10925-10930. https://pubmed.ncbi.nlm.nih.gov/18676614/
2. Dahan A, Dunne A, Swartjes M, et al. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med. 2013;19(1):334-345. https://pubmed.ncbi.nlm.nih.gov/24136731/
3. Brines M, Dunne AN, van Velzen M, et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Mol Med. 2015;20(1):658-666. https://pubmed.ncbi.nlm.nih.gov/25387363/
4. Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain. Invest Ophthalmol Vis Sci. 2017;58(6):BIO52-BIO60. https://pubmed.ncbi.nlm.nih.gov/28475703/

Published Studies