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ARA-29011 residuesQEQLERALNSSEach bubble = one amino acid. Size = residue mass. Color = chemical class.Also known as: cibinetide, ARA 290, ARA-290
Twenty-three percent more corneal nerve fibers in 28 days. ARA-290 (cibinetide) is an 11-amino-acid peptide engineered from erythropoietin's helix B surface. It selectively activates the innate repair receptor (IRR) without stimulating red blood cell production. Phase 2b data from 64 sarcoidosis patients showed structural nerve fiber regeneration, not symptom suppression. The program earned FDA Orphan Drug and Fast Track designations, though no Phase 3 has been registered. Neuropathy patients and clinicians consider ARA-290 one of the most mechanism-validated repair peptides available through research channels.
Twenty-three percent improvement in corneal nerve fiber area after just four weeks of daily injections. That result came from Dahan and colleagues' Phase 2b trial of 64 sarcoidosis patients [1]. It put ARA-290 on the map for small fiber neuropathy. ARA-290, also called cibinetide (CAS 1208243-50-8), is an 11-amino-acid synthetic peptide modeled on erythropoietin's helix B surface domain. ARA-290 binds the innate repair receptor (IRR), a heterodimer of the EPO receptor and CD131. That receptor sits on neurons, Schwann cells, and immune cells. Activation triggers JAK2/STAT5 and PI3K/Akt signaling, which promotes cell survival, suppresses TNF-alpha and IL-6, and supports nerve fiber regeneration. The key distinction from EPO itself: ARA-290 doesn't touch the homodimeric EPOR responsible for making red blood cells. No polycythemia risk. No thrombosis concern. In practice, neuropathy patients with sarcoidosis or type 2 diabetes make up the primary user base. The clinical protocol is straightforward: 4 mg subcutaneous once daily for 28 days. Community experience, though limited to fewer than 50 dedicated threads, tracks closely with trial data. Users describe burning and tingling improvements starting around week two, with benefits persisting months after the cycle ends. ARA-290 holds FDA Orphan Drug and Fast Track designations for sarcoidosis-associated small fiber neuropathy. A second Phase 2 trial in type 2 diabetic neuropathy showed HbA1c reduction and PainDetect score improvement (Brines et al.)[2]. The honest limitation: Araim Pharmaceuticals appears to have gone quiet since 2017, and no Phase 3 trial has been registered.
Erythropoietin does two things: it makes red blood cells and it protects tissues from damage. ARA-290 was engineered to do only the second part. The peptide's 11-amino-acid sequence mirrors a specific surface region (helix B) of the EPO molecule. That surface binds the innate repair receptor, a heterodimer of the EPO receptor subunit (EPOR) and CD131 (the beta common receptor). When ARA-290 locks onto the IRR, it kicks off JAK2/STAT5 and PI3K/Akt signaling. These pathways block apoptosis in damaged cells and suppress pro-inflammatory cytokines, specifically TNF-alpha, IL-6, and IL-1beta. NF-kB-mediated cell death signals get dialed down. In peripheral nerves, the result is Schwann cell survival and small nerve fiber regeneration. There's a pain component too. ARA-290 modulates TRPV1 channels at the nociceptor level (confirmed in preclinical work)[3]. This reduces nociceptive signaling independent of anti-inflammatory effects. The selectivity is the whole point. ARA-290 doesn't activate the homodimeric EPOR that drives erythropoiesis. Three Phase 2 trials confirmed no changes in hemoglobin, hematocrit, or reticulocyte count. You get the tissue protection without the blood thickening that makes EPO dangerous outside of anemia.
Phase 2b positive for sarcoidosis-associated small fiber neuropathy (SFN): 4 mg SC daily × 28 days produced significant corneal nerve fiber regeneration (+23% CNFA vs placebo) and neuropathic pain reduction. Positive Phase 2 data also exist for type 2 diabetic neuropathy (HbA1c ↓, PainDetect ↓) and diabetic macular edema. No Phase 3 registered as of April 2026.
Culver/Dahan et al. 2017 IOVS (PMID 28475704): Phase 2b, n=64 sarcoidosis-SFN patients; 4 mg arm met primary endpoint for CNFA and CNFD improvement vs placebo.
Small Phase 2 trials (n≤64); no registered Phase 3; sponsor (Araim Pharmaceuticals) appears dormant since 2017 with no new funding or press releases; no comparative trials vs. standard neuropathy therapies; long-term safety beyond 28 days not formally characterized.
Positive among niche SFN and sarcoidosis users. Very limited community footprint (<50 dedicated Reddit threads). Users report meaningful pain relief lasting weeks to months post-cycle, consistent with clinical trial findings.
Community closely mirrors clinical trial protocol: same 4 mg dose, same 28-day duration, same SC route. No dose escalation beyond trial doses. Stacking practices (BPC-157, TB-500) are community-only but do not conflict with clinical guidance.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 1mg | Daily |
| Moderate | 2mg | Daily |
| Aggressive | 4mg | Daily |
Reconstitution math first. A 10 mg vial with 2 mL bacteriostatic water gives you 5 mg/mL. At the clinical dose of 4 mg, that's 0.8 mL, or 80 units on a U-100 insulin syringe. One vial lasts 2.5 days at 4 mg/day. You'll need 11 to 12 vials for a full 28-day course. A 5 mg vial with 2 mL BAC water gives 2.5 mg/mL. At 4 mg, that's 1.6 mL per injection, which is too much volume for a comfortable single SC shot. Stick with 10 mg vials if you're running the full clinical dose. Starting at the conservative 1 mg dose? That's 0.2 mL (20 units), and a single 10 mg vial covers 10 days. The 20-minute plasma half-life sounds short, but it's the wrong thing to focus on. ARA-290 clears fast from blood, but the downstream gene expression changes through JAK2/STAT5 persist for hours. Once-daily dosing is sufficient; don't split the dose. Store reconstituted vials at 2 to 8 degrees C. Use within 2 to 3 weeks. Budget before you start. Mid-cycle supply interruption is common and kills the protocol. A clinical-equivalent course at 4 mg/day costs $672 to $1,008 at current research-grade pricing.
Clinical trials used daily SC injections for 28 days (4 weeks). Follow with a 2-week washout before repeating. Assess nerve function and pain scores between cycles.
The 28-day cycle is derived directly from clinical trial design, not from mechanistic receptor desensitization data. The off-period serves three purposes: (1) assessment of structural nerve fiber regeneration response before committing to a second course; (2) monitoring for late AEs including LFT changes; (3) theoretical gap to reduce anti-drug antibody (ADA) risk with repeat protein/peptide exposure, though no ADA data exist for ARA-290 specifically.
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Expected: Some reduction in neuropathic pain scores by week 4; corneal nerve fiber improvement less robust than 4 mg arm in trials
Monitor: Weekly NRS/pain diary; CBC at baseline and end of cycle
Roll gently, don't shake. This gives you 5 mg/mL.
Draw 0.8 mL (80 units on a U-100 insulin syringe) for a 4 mg dose. For the 1 mg beginner dose, draw 0.2 mL (20 units). For 2 mg, draw 0.4 mL (40 units).
Anterior thigh is the trial-validated site. Abdomen works too. Rotate sides daily.
Inject subcutaneously at a 45-degree angle using a 28 to 31 gauge insulin needle. Push the plunger slowly.
No timing requirement relative to meals or sleep.
Assess pain levels and nerve function during the 2-week washout. Repeat the cycle only if further improvement is warranted.
Discard after 2 to 3 weeks. A single 10 mg vial covers roughly 2 days at 4 mg/day, so reconstitute a fresh vial every 2 to 3 days.
2 mg IV 3×/week in pilot vs. 4 mg SC daily in Phase 2b
IV protocol from earlier pilot study; Phase 2b validated SC daily as the primary route. IV provides faster Cmax (~3 ng/mL more rapidly) but IV access requirement and lower frequency may reduce IRR signaling continuity. Not recommended over SC daily.
Complementary tissue repair stack: TB-500 promotes vascularization and actin upregulation; ARA-290 drives nerve fiber regeneration via IRR. Community reports enhanced recovery in neuropathy with concurrent nerve and vascular repair.
TB-500 2 mg SC 2–3×/week concurrent with ARA-290 28-day cycle
Nerve repair stack: BPC-157 provides broader regenerative and anti-inflammatory effects (GI, systemic); ARA-290 provides IRR-specific nerve fiber regeneration. Mechanistically distinct and non-competing.
BPC-157 500 mcg SC daily concurrent with ARA-290 cycle
Combined neuroprotective/regenerative profile; GHK-Cu provides anti-inflammatory and growth factor support; less established as a stack but cited in advanced neuropathy protocols.
Both ARA-290 and EPO target EPO receptor subunits. ARA-290 selectively activates IRR (EPOR/CD131 heterodimer); EPO activates homodimeric EPOR. Concurrent use may cause excessive or unpredictable receptor cross-activation across both receptor complexes.
Do not combineIRR signaling has pro-angiogenic and tissue-repair components; anti-VEGF agents may partially oppose ARA-290 efficacy in the DME indication and theoretically reduce tissue-repair signaling in other contexts.
Pricing updated 2026-04-09
The most important safety question with any EPO-derived compound: does it raise red blood cell counts? For ARA-290, the answer is consistently no. Three separate Phase 2 trials tracked hemoglobin, hematocrit, and reticulocyte counts. None showed changes from baseline. That's the core safety advantage, and the data backs it up. Active malignancy is a serious theoretical concern. ARA-290 activates anti-apoptotic signaling via JAK2/STAT5 and PI3K/Akt. In tissue with existing malignant growth, suppressing programmed cell death could theoretically accelerate tumor progression. Phase 2 trials excluded patients with active cancer. Anyone with a current or recent cancer diagnosis should avoid ARA-290. The most commonly documented adverse event across all trials is injection site reactions. Mild redness and soreness at the SC injection site. This tracks with 28 consecutive daily injections into the same general area. Rotating between anterior thigh and abdomen helps. A 28 to 31 gauge insulin needle minimizes tissue trauma. Liver function bears watching. Mild elevations in ALT and AST appeared at low frequency in Phase 2 data. For most users this won't matter. But if you have pre-existing hepatic conditions, get LFTs before starting and before each repeat cycle. The threshold to stop: ALT or AST above 3 times the upper limit of normal. Headache has been noted at low frequency. Transient, not dose-dependent in the available data. Mild dizziness and occasional nausea round out the observed side effect profile from published trials. The honest gap in the safety profile is duration. No trial ran beyond 28 days. Long-term effects of IRR activation, repeated cycling, and cumulative exposure are unknown. Anti-drug antibody (ADA) formation is a theoretical risk with any peptide given repeatedly; no ADA testing was performed in ARA-290 trials. Concurrent use with EPO or erythropoiesis-stimulating agents is contraindicated due to overlapping receptor pathways. Strong immunosuppressants (tacrolimus, cyclosporine, biologics) warrant increased monitoring because of additive immune modulation. Anti-VEGF therapies (bevacizumab, ranibizumab) may oppose the tissue-repair and angiogenic components of IRR signaling. Pregnancy and breastfeeding are absolute contraindications; no reproductive safety data exist. Children and adolescents lack pediatric safety data. The total human exposure in published trials is roughly 120 to 150 patients across Phase 1, 2, and 2b studies. That's enough to establish a short-term safety signal but far short of the thousands needed for rare adverse event detection. Keep that context in mind. When to seek medical attention: worsening injection site reactions that escalate rather than stabilize; signs of hepatic dysfunction including nausea, jaundice, or right upper quadrant pain; any hypersensitivity symptoms such as urticaria or dyspnea. Stop ARA-290 and consult a physician immediately.
Verify ARA-290 dosing and safety with a second opinion
Niche compound with limited vendor market. Fewer HPLC-verified sources than mainstream peptides. Underdosing risk is real given high per-mg cost creating incentive for dilution. Some early-market pricing ($2–4/mg) may reflect lower-purity product. TFA content in non-TFA-removed batches is a secondary concern for daily SC injections over 28 days.
| Test | When | Target |
|---|---|---|
| NRS / pain diary | Weekly throughout cycle (baseline, week 1, 2, 3, 4) | — |
| CBC with differential | Baseline and end of 28-day cycle | No change from baseline in Hgb, Hct, reticulocyte count |
| Liver function tests (ALT, AST, bilirubin) | Baseline; repeat before each new cycle if cycling | ALT/AST < 3× ULN |
| HbA1c | Baseline and 4–6 weeks post-cycle (diabetic neuropathy indication) | — |
| Corneal confocal microscopy (CNFL/CNFD) | Baseline and 8–12 weeks post-cycle (if available) | — |
Primary subjective efficacy endpoint matching Phase 2 trial methodology; used to assess response and inform repeat-cycle decision
Confirm absence of erythropoietic effect (hemoglobin, hematocrit, reticulocyte count); three Phase 2 trials found no changes but monitoring is prudent for long-term or repeat users
Mild LFT elevation noted at low frequency in Phase 2 trials; relevant for users with pre-existing hepatic conditions
Phase 2 in T2DM showed HbA1c reduction; monitoring captures metabolic benefit and assists diabetic management adjustments
Objective measure of small nerve fiber density; primary endpoint in Phase 2b NCT02039687; quantifies structural response beyond subjective pain scores
IRR signaling pathways activated. Anti-inflammatory cytokine modulation begins. No visible changes expected yet. Some patients report mild reduction in neuropathic pain intensity.
Measurable reduction in neuropathic pain scores observed in clinical trials. Anti-inflammatory effects established. Early nerve fiber regenerative processes underway at the cellular level.
End of standard clinical trial cycle. Corneal nerve fiber density increases documented (approximately 23% in the 4 mg group). Meaningful pain reduction in patients with moderate to severe baseline pain. Improved functional activity correlated with nerve fiber regeneration.
Nerve fiber regeneration effects may persist beyond the dosing period due to structural repair. Assess pain levels and nerve function. Consider repeating cycle after 2-week washout if further improvement is needed.
Days 1 to 7: IRR activation, no visible change IRR signaling kicks in fast. Plasma half-life is only 20 minutes, but that's just the peptide clearing, not the signal stopping. JAK2/STAT5 and PI3K/Akt activation downstream persists for hours after each injection. Anti-inflammatory cytokine suppression (TNF-alpha, IL-6, IL-1beta) starts building. TRPV1 modulation at nociceptors begins. Don't expect to feel anything yet. Some users notice a faint reduction in baseline pain intensity. The main experience at this stage is mild injection site soreness. Weeks 2 to 3: Initial symptom reduction This is when the first real change shows up. Phase 2b documented measurable NRS pain score reductions at this interval. The anti-inflammatory cascade is fully established. At the cellular level, Schwann cell survival is improving and small nerve fibers are starting to sprout. Users flag the first noticeable drop in burning, tingling, and numbness. Sleep often improves as a secondary effect of reduced pain. If you're thinking "this isn't working" at day 10, give it more time. Week 4: Peak response, end of clinical protocol End of the standard clinical protocol. Phase 2b primary endpoints landed here: 23% increase in corneal nerve fiber area (CNFA) in the 4 mg group versus placebo. Intraepidermal nerve fiber density (IENFD) also improved. NRS pain scores dropped meaningfully. In the diabetic neuropathy cohort, HbA1c decreased and PainDetect scores came down. Community users describe improved daily function and, in some cases, return of sensation in areas that had gone numb. Post-cycle (weeks 5 to 16+): Sustained benefit from structural regeneration The results stick around. Nerve fiber improvements persist because the regeneration is structural, not based on ongoing receptor occupancy. Follow-up data from Phase 2b showed maintained corneal nerve density weeks after the last injection. Community users describe pain relief lasting 4 to 6 months from a single 28-day course. That persistence is what separates ARA-290 from symptom-masking approaches. If symptoms return, most users re-dose 3 to 6 months later.
Rapid plasma clearance (t½ ~20 min); downstream JAK2/STAT5 and PI3K/Akt signaling initiated; anti-inflammatory cytokine suppression (TNF-α, IL-6, IL-1β) begins; TRPV1 channel modulation at nociceptor level.
Typically no perceptible change. Occasional mild reduction in baseline pain intensity reported by some users. Injection site soreness (mild) is the most commonly noted experience.
Measurable NRS pain score reduction documented in Phase 2b at this interval. Anti-inflammatory cascade established. Early Schwann cell survival and small nerve fiber sprouting at the cellular level.
First noticeable reduction in burning, tingling, and numbness. Sleep improvement secondary to pain reduction. Users who report "it's not working" at this stage are advised to continue.
Phase 2b primary endpoints: +23% corneal nerve fiber area (CNFA) in 4 mg arm vs placebo; significant intraepidermal nerve fiber density (IENFD) improvement; NRS pain reduction maintained. Diabetic neuropathy cohort: HbA1c ↓, lipid improvement, PainDetect score ↓.
Meaningful pain reduction with improved daily function. Some users report return of sensation in previously numb areas. Metabolic improvements noted by users with concurrent diabetic neuropathy.
Nerve fiber improvements persist beyond dosing period due to structural regeneration (not receptor occupancy). Follow-up data in Phase 2b showed maintained corneal nerve density weeks post-cycle.
Pain relief reported lasting 4–6 months after a single 28-day course. Community considers this the key differentiator from symptom-masking approaches. Re-dosing prompted by symptom recurrence, typically 3–6+ months post-cycle.
Source: Human PK: plasma t1/2 ~20 minutes after 4 mg SC (Brines et al., Mol Med 2015, PMID 25569804). Peak plasma ~3 ng/mL. Rapid clearance, but downstream IRR-mediated gene expression changes persist for hours.
Loading the interactive decay curve.
ARA-290 (cibinetide) is not FDA-approved for any indication. It holds FDA Orphan Drug Designation and Fast Track Designation for sarcoidosis-associated small fiber neuropathy. The European Medicines Agency (EMA) also granted Orphan Drug Designation. These designations reflect regulatory interest in an unmet need, not approval. The compound is available through research chemical vendors as a lyophilized peptide. It is not available through compounding pharmacies or as a prescribed medication. Sourcing is limited; fewer vendors carry ARA-290 compared to mainstream compounds. Possession for personal research use varies by jurisdiction. ARA-290 is derived from erythropoietin's structure but does not stimulate erythropoiesis. Athletes subject to anti-doping testing should verify current WADA prohibited lists, as EPO-derived peptides may fall under S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). This content is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. Consult a qualified healthcare provider before using any research compound. ARA-290 has not been evaluated for safety or efficacy by any regulatory agency for therapeutic use.
Peptide Schedule Research TeamReviewed Apr 20267 Citations
