ARA-290

ARA-290 (also called cibinetide or pyroglutamate helix B surface peptide) is an 11-amino-acid peptide engineered from helix B of erythropoietin (EPO), the hormone that normally drives red blood cell production ⁷. It binds the innate repair receptor (IRR), a receptor pair that healthy tissue barely expresses but that injury, inflammation, or low oxygen turns on rapidly ²⁰. That makes ARA-290 a conditional repair signal rather than a constant stimulant.

Research has concentrated on nerve damage and neuropathic pain ²¹, injury-related tissue protection ⁷, and transplant support ¹⁴. Human studies are small and early-phase; the most frequently tested human dose is 4 mg by subcutaneous injection once daily ¹⁶. The compound is not FDA-approved for any use ¹.

ARA-290 binds only to the innate repair receptor (IRR), a heterodimer made of the EPO receptor (EPOR) and the β-common receptor (CD131/βcR). Healthy tissue shows little IRR, but damaged or inflamed tissue turns it on ⁷. Because the peptide does not activate the EPOR homodimer that EPO uses for red cell production, it separates repair signaling from blood cell effects ³.

Inside cells, the dominant pathway is PI3K/Akt, which supports cell survival and repair, rather than the JAK2/STAT5 pathway linked to red cell production ²⁰. The result is less inflammation, less oxidative stress, and less programmed cell death (apoptosis) in stressed tissue ⁷.

• In nerve injury models, the effect depends on βcR: mice missing βcR lose the analgesic response, and blocking βcR in stroke-model mice removes neuroprotection ⁶.
• In Schwann cells, ARA-290 reduces NLRP3 inflammasome activation, a key inflammatory switch ⁴.
• In pain research, part of the effect may involve the TRPV1 channel, linking immune signaling to nerve sensitivity ¹⁹.

A distinguishing feature is the half-life: it clears from plasma in about two minutes, yet one short course can change inflammatory cell behavior for weeks ²⁰.

ARA-290's evidence base is broad but mixed in size; the strongest human support is in nerve-related symptoms, while most mechanistic and efficacy data come from animals and cell studies.

• Neuropathic pain and small-fiber repair: In spared nerve injury rats, 3 to 60 µg/kg produced dose-dependent relief of mechanical and cold allodynia lasting up to 20 weeks, with a parallel reduction in spinal microglia activation ²². In human sarcoidosis studies, symptom scores improved and corneal nerve fiber density increased ¹⁷. In a type 2 diabetes study, patients improved neuropathic symptom scores and metabolic control ²¹.
• Kidney protection: In cell and animal models, ARA-290 reduced oxidative stress, inflammation, and apoptosis from cisplatin toxicity, and improved survival in a hemolytic-uremic syndrome mouse model without thromboembolic events ⁷.
• Heart protection: In a 15-month randomized rat study, chronic treatment reduced cardiac inflammation, preserved ejection fraction, and blunted age-related blood pressure rise ⁸.
• Metabolic effects: Goto-Kakizaki diabetic rats improved insulin release and glucose tolerance ¹⁸. Diabetic db/db mice improved insulin sensitivity but not executive cognitive flexibility ².
• Islet transplant support: In human islet stress models, cibinetide preserved ATP and reduced cell death; in mice, a 14-day course with low-dose tacrolimus improved long-term graft survival ¹⁴.
• Bone: One month in mice raised cortical and trabecular bone mineral density by about 5 to 6 percent and inhibited osteoclast formation ¹².
• Negative result: In a 9-patient Phase 2 diabetic macular edema trial, 12 weeks of 4 mg/day did not improve visual acuity or retinal thickness, though patient-reported vision scores improved slightly ¹⁶.

Human trial protocols have used a flat 4 mg subcutaneous dose once daily, without weight-based adjustment. The Phase 2 diabetic macular edema study ran this schedule for 12 weeks with no serious adverse events ¹⁶. A pilot randomized trial in sarcoidosis-associated small-fiber neuropathy used daily subcutaneous dosing; the published abstracts do not report the exact treatment duration ²³, and type 2 diabetes studies used daily subcutaneous courses ²¹. A 4-week open-label study in rheumatoid arthritis reported safety and efficacy signals ⁴⁵.

Animal protocols are different in scale and route. Examples include 30 µg/kg by intraperitoneal injection on an intermittent schedule in nerve injury models ²², 60 µg/kg twice weekly for 10 months in post-heart-attack rats ³⁴, and 120 µg/kg daily for 14 days in mouse islet transplantation ¹⁵. Those microgram-per-kilogram animal doses are not directly scalable to human dosing.

No weight-stratified human data exist. The flat 4 mg dose works out to about 50 µg/kg for an 80 kg adult, but trials did not adjust by body weight ¹⁶. Community research protocols usually mirror the clinical dose, with 2 to 4 mg once daily, sometimes split twice daily, and 28-day courses. A representative community pattern is shown in the timeline card on this page.

ARA-290 is supplied as a freeze-dried (lyophilized) powder. Standard research handling uses bacteriostatic water, which contains 0.9% benzyl alcohol, or sterile water for injection as the diluent. Add the diluent slowly down the vial wall and swirl gently; avoid shaking or vortexing, since mechanical stress can damage the peptide.

Storage before reconstitution: keep unopened vials at -20°C for long-term stability, or refrigerated for short-term storage. After reconstitution, keep the solution refrigerated at 2-8°C and protected from light. Do not refreeze the reconstituted solution, because repeated freeze-thaw cycles degrade the peptide. Research practice is to use the solution within 14 to 30 days and to discard it if it becomes cloudy or contains particles.

A human Phase 2 trial used daily subcutaneous self-administration for 12 weeks, establishing the reconstituted injectable route in a clinical setting ¹⁶. Use the calculator below for exact dilution quantities.

No formal pharmacokinetic drug-interaction studies have been published for ARA-290. The known and likely interactions below come from mechanism research, animal models, and cell studies.

• EPO and ESAs: ARA-290 and EPO use different receptor complexes. In mice, combining ARA-290 with EPO reduced EPO-driven osteoclast progenitor expansion, and ARA-290 alone increased bone mineral density ¹².
• Tacrolimus: In mouse islet transplantation, cibinetide plus low-dose tacrolimus improved long-term graft survival better than either treatment alone ¹⁵.
• Cisplatin and doxorubicin: In cell studies, ARA-290 reduced genotoxic and oxidative damage from both drugs ⁷. Because the protection extended to a liver cancer cell line, concurrent cancer treatment is a caution, not a known benefit.
• Glucose-lowering drugs: ARA-290 improves insulin release and glucose tolerance in diabetic rats ¹⁸ and metabolic control in a small human study ²¹. Additive glucose lowering is plausible.
• Antihypertensives: In a rat preeclampsia model, the peptide reduced systolic and diastolic blood pressure ³¹. Additive blood pressure lowering is plausible but untested in humans.
• Supplements: Antioxidant or anti-inflammatory supplements such as alpha-lipoic acid, omega-3, and curcumin have overlapping mechanisms but no direct interaction studies ⁷.

In animal research, intermittent dosing gave long-lasting effects. Five 30 µg/kg doses every other day, followed by weekly injections, produced pain relief persisting 15 to 20 weeks after the last dose ²². This persistence is attributed to a long-lived change in inflammatory cell signaling, not to drug remaining in the body ²⁰.

Human trials used fixed courses rather than open-ended treatment: 4 weeks in rheumatoid arthritis ⁴⁵ and 12 weeks in diabetic macular edema ¹⁶; the published abstracts do not report the exact sarcoidosis small-fiber neuropathy duration, though about 28 days is a community protocol duration ²³. No human data cover continuous use beyond 12 weeks ¹⁶.

Community research protocols pair these on-periods with off-periods. A common pattern is 20 to 30 days on, followed by 2 to 4 weeks off. An alternative starts with 4 mg daily for 10 days, then 4 mg two to three times per week. Retreatment is typically guided by symptom recurrence rather than a fixed calendar.

Because the repair receptor is induced mainly in damaged tissue, cycling aligns dosing with periods when the receptor is present ²⁰. ARA-290 does not raise red blood cell counts, so off-periods are not required to avoid polycythemia ²⁰.

ARA-290 acts through the innate repair receptor, so it overlaps conceptually with other tissue-protective peptides but uses a different signaling route ⁷. No controlled human studies test ARA-290 in a peptide stack.

• BPC-157: Different receptor targets; community protocols sometimes combine the two for soft-tissue and nerve repair, but no published co-use data exist.
• TB-500: Shares a tissue-protective profile but works through different pathways. Co-use is community-documented and unstudied.
• GH secretagogues such as ipamorelin: Distinct signaling systems with no expected direct conflict; combination data are absent.
• GLP-1 receptor agonists: Theoretical synergy on glucose control and neuropathy endpoints, since ARA-290 improves metabolic endpoints in diabetic models ¹⁸. Glucose monitoring is part of this rationale.
• EPO and ESAs: ARA-290 is not a simple substitute for EPO in all settings, but animal data suggest co-treatment can blunt EPO-driven bone loss ¹².
• CHBP: A stabilized cyclic analogue of the same helix B peptide family. Research treats it as a pharmacokinetic improvement of the same IRR target, not a complementary stack ⁵.

ARA-290 (cibinetide) is not FDA-approved or EMA-approved for any indication, and no Phase 3 trial has been completed ¹. It is not scheduled under the U.S. Controlled Substances Act. U.S. access is limited to research-grade material and compounding exemptions; neither route confers FDA approval for human use.

Development history is real but small: a randomized double-blind pilot in sarcoidosis small-fiber neuropathy ²⁴, open-label sarcoidosis follow-up ²³, type 2 diabetes studies ²¹, a 4-week open-label rheumatoid arthritis study ⁴⁵, and a Phase 2 diabetic macular edema trial under the name cibinetide ¹⁶.

For sport, ARA-290 is not explicitly named on the WADA Prohibited List. Because it lacks marketing approval, the WADA category S0 standard for non-approved substances applies, which is prohibited at all times in and out of competition. No athlete sanction history involving ARA-290 is documented in the available evidence.

ARA-290's central safety property is that it does not stimulate red blood cell production. Across species and studies, hemoglobin, hematocrit, and red cell counts stay stable, avoiding the thrombosis risk associated with full EPO ¹⁰. In a Phase 2 trial with 4 mg daily for 12 weeks, no serious adverse events and no anti-drug antibodies were reported ¹⁶.

Reported and theoretical side effects:

• Injection-site reactions: Mild redness or stinging is the most commonly reported practical effect; frequency is not formally quantified ¹⁶.
• Signs of serious injection complications: Seek medical care for spreading redness, warmth, swelling, or pain at the injection site (possible abscess or cellulitis) or for signs of an allergic reaction such as hives, facial or throat swelling, difficulty breathing, or feeling faint.
• Fatigue: Transient fatigue after dosing is anecdotally reported and not captured in published datasets.
• Blood pressure and glucose changes: Animal data show blood pressure lowering in preeclampsia ³¹ and better glucose handling in diabetic models ¹⁸. Additive effects with antihypertensives or diabetes drugs are possible.
• Immune remodeling: ARA-290 shifts monocytes and macrophages toward repair phenotypes; no infection signal appeared in human studies ⁷.
• Chemoprotection concern: In cells, the peptide protected against cisplatin and doxorubicin toxicity, including a cancer cell line, so concurrent chemotherapy is a relative caution ⁷.

Main unknowns: human safety data stop at 12 weeks ¹⁶, reproductive safety is untested, no formal drug interaction studies exist, and long-term immune consequences are uncharacterized ¹¹.