Ara-290
What do these badges mean?
Evidence tier
- AHuman-validated — Human trials showing positive results and good safety.
- BAnimal-grade — No human trials yet, but solid animal/preclinical evidence of effect and safety.
- CAnecdotal — No human or animal trials — only anecdotal/observational reports.
- DInsufficient evidence — No or insufficient evidence (encyclopedia only — never recommended by the builder).
Safety light
- 🟢 Green — Only mild, manageable side effects; reasonable safety data.
- 🟡 Yellow — Needs active management, has a meaningful contraindication/interaction, or has thin long-term data.
- 🔴 Red — Risk of a hospital-level event — treat with serious caution.
Browse-only — not on the protocol builder's curated shortlist, so the builder won't recommend it.
What is it?
ARA-290 is the cleanest piece of peptide engineering in the endogenous-protection cluster. The story starts with a discovery that rewrote what EPO actually does.
EPO (erythropoietin) is famous as the blood-doping hormone — what Lance Armstrong used, what raises red blood cell counts, what creates hematocrit, thrombosis, and stroke risk. But Brines and Cerami at Araim Pharmaceuticals found that EPO actually operates through two entirely different receptor systems with entirely different jobs:
- The blood-building receptor — the classical EPOR homodimer (two identical EPO receptor subunits, symmetrical). This is the one everybody knew about. Drives erythropoiesis. Raises hematocrit.
- The tissue-repair receptor — the Innate Repair Receptor (IRR): a heterodimer of two different subunits, EPOR + CD131 (the β common receptor, βcR). A mismatched pair. When EPO binds this one, it tells the cell: survive, repair yourself, calm the inflammation. No red blood cell production at all.
The engineering insight was to identify exactly which surface of the EPO molecule activates the IRR — a specific patch called the “helix-B face.” Brines and Cerami carved that surface out and rebuilt it as a standalone 11-amino-acid peptide. The repair signal, isolated and concentrated. That’s ARA-290.
Why this matters: ARA-290 only fits the IRR — its shape specifically matches the gap between the two different subunits of the heterodimer. It physically cannot dock at the classical EPO homodimer. The result is a peptide that is non-erythropoietic — it does not and cannot raise red blood cell count. EPO’s entire hematological risk profile is engineered out. What remains is a clean tissue-protective signal with a published Phase 2 RCT and FDA Orphan Drug Designation behind it.
How can it help me?
Best fit for: Heal injuries & recover, Sharper mind, focus & mood. Here's what Ara-290 is studied for and how strong that evidence is — the practical view above covers what it is and how it works.
The full evidence — every human, animal, and lab study, graded — is one tap away: use the See the deeper science → toggle at the top.
Is it dangerous? What are the side effects?
Regulatory status:
- FDA Orphan Drug Designation for neuropathic pain in sarcoidosis — granted; meaningful regulatory advance. The FDA reviewed the data and acknowledged real potential benefit for a serious rare disease. Opens fast-track development pathways.
- Full FDA approval: never submitted. Development program never reached Phase 3.
- Araim Pharmaceuticals: closed as of 2026. Not a clinical failure — a financing failure. A small biotech couldn’t fund Phase 3 for niche indications; peptides are expensive to manufacture. Economics ended the company; the biology didn’t fail. The Brines/Cerami dual-receptor discovery and the published Phase 2 data remain in the scientific record regardless of the company’s fate.
- Post-closure status: patents may be expired; the molecule could be picked up by another developer. Orphan Drug precedents for molecule recovery exist.
- WADA: non-erythropoietic by design — cannot raise red blood cell count; sidesteps EPO prohibition entirely
Part 1 — How to reconstitute it
What you'll need: bacteriostatic water (sterile, preserved water you mix the powder with) and a separate, larger reconstitution syringe just for mixing — not the small syringe you inject with.
Storage: refrigerated lyophilized; reconstitute with bacteriostatic water; ~30 days post-reconstitution
How to mix it
- Tilt the vial and let the bacteriostatic water run slowly down the inside glass wall — never squirt it straight onto the powder.
- Swirl gently to dissolve. Never shake — shaking can damage the peptide.
- Store the reconstituted vial refrigerated and out of light.
- Use it within the beyond-use window your source specifies — reconstituted peptides are commonly used within a few weeks; confirm the window for your specific peptide.
Use the free reconstitution calculator to turn any vial size + water volume into exact units on an insulin syringe.
Part 2 — Typical dosing
Talk to your medical provider before starting any protocol. That said, here are the doses most people commonly use — shared for educational purposes so you can have an informed conversation. These peptides are sold for research use only and are not FDA-approved drugs, and this isn't medical advice.
The syringe. Use a 0.3 mL U-100 insulin syringe — it's sized for these small subcutaneous doses. Inject subcutaneously (into the fat just under the skin) and rotate injection sites.
Trial-validated dose:
- 4 mg SubQ injection daily × 28 days — the dose from both Brines 2015 (T2D neuropathy) and the sarcoidosis SFN trial
- Reconstitution example: 4 mg vial + 1 mL bacteriostatic water = 4 mg/mL; a 4 mg dose = 1 mL = 100 units on a U-100 insulin syringe (a full syringe)
Community / anti-aging dosing (not formally validated):
- 0.5–1 mg SubQ daily, or 1–2 mg every other day
- Well below the trial dose; used in the biohacker community as a “longevity / nerve maintenance” pattern
- No published data validates this range — it’s extrapolation from the trial dose and general peptide community practice
Cycle: 28-day blocks are the trial-validated pattern. Extended dosing past 28 days lacks published data. The slow-repair timeline (weeks 4–8 for meaningful symptom change) means a 28-day course starts showing benefits near its own end — a longer block or repeated cycles is the logical extension for chronic neuropathic conditions, but it’s not formally studied.
What should I avoid combining — and what's synergistic?
Ara-290 doesn't have a dedicated stacking protocol in our notes — the interactions that matter most are in the safety section above. For how people combine it with other peptides, the deeper-science view has the full detail.
How can I buy this?
Ara-290 is available from US Pure Peptides — use code OHM20 for 20% off. US-manufactured, ISO 17025-accredited third-party COA testing on every batch, free bacteriostatic water included.
Ara-290 is also available from BioLongevity Labs — use code OHM-15 at BioLongevity for 15% off. As always, buy only from a source that publishes third-party Certificates of Analysis (COAs) confirming identity and >99% purity.
When you use my coupon code to buy peptides with these sellers, you enjoy a discount off retail price, and I make a small commission which helps me to continue to offer this peptide educational site to you for free. I only have affiliate relationships with peptide manufacturers that show evidence that their peptides are 100% manufactured in the US, 3rd party lab tested for purity, transparent COAs posted on their websites, and that have good customer service.
| Full names | ARA-290; cibinetide |
| Class | 11-amino-acid synthetic peptide engineered from EPO’s tissue-protective domain |
| Origin | Rationally designed by Michael Brines & Anthony Cerami (Araim Pharmaceuticals) from EPO’s helix-B face |
| Primary receptor | Innate Repair Receptor (IRR) — EPOR + CD131 (βcR) heterodimer |
| Does NOT activate | Classical EPO homodimer; non-erythropoietic |
| Signaling cascade | STAT3 → PI3K → Akt → anti-apoptotic gene expression |
| Primary use cases | Peripheral neuropathy (diabetic, sarcoidosis SFN); nerve repair; anti-inflammatory |
| Route | Subcutaneous self-injection |
| Trial-validated dose | 4 mg SubQ daily × 28 days (Brines 2015; sarcoidosis SFN trial) |
| Half-life in blood | Under 1 hour (kidneys filter rapidly) |
| FDA status | Orphan Drug Designation for neuropathic pain in sarcoidosis; never reached full approval |
| Company status | Araim Pharmaceuticals closed 2026 |
| Vendor (OHM primary) | US Pure Peptides — code OHM20 for 20% off |
| WADA | Non-erythropoietic; not banned |
What it is
ARA-290 is the cleanest piece of peptide engineering in the endogenous-protection cluster. The story starts with a discovery that rewrote what EPO actually does.
EPO (erythropoietin) is famous as the blood-doping hormone — what Lance Armstrong used, what raises red blood cell counts, what creates hematocrit, thrombosis, and stroke risk. But Brines and Cerami at Araim Pharmaceuticals found that EPO actually operates through two entirely different receptor systems with entirely different jobs:
- The blood-building receptor — the classical EPOR homodimer (two identical EPO receptor subunits, symmetrical). This is the one everybody knew about. Drives erythropoiesis. Raises hematocrit.
- The tissue-repair receptor — the Innate Repair Receptor (IRR): a heterodimer of two different subunits, EPOR + CD131 (the β common receptor, βcR). A mismatched pair. When EPO binds this one, it tells the cell: survive, repair yourself, calm the inflammation. No red blood cell production at all.
The engineering insight was to identify exactly which surface of the EPO molecule activates the IRR — a specific patch called the “helix-B face.” Brines and Cerami carved that surface out and rebuilt it as a standalone 11-amino-acid peptide. The repair signal, isolated and concentrated. That’s ARA-290.
Why this matters: ARA-290 only fits the IRR — its shape specifically matches the gap between the two different subunits of the heterodimer. It physically cannot dock at the classical EPO homodimer. The result is a peptide that is non-erythropoietic — it does not and cannot raise red blood cell count. EPO’s entire hematological risk profile is engineered out. What remains is a clean tissue-protective signal with a published Phase 2 RCT and FDA Orphan Drug Designation behind it.
How it works — mechanism
Receptor targeting
After SubQ injection, ARA-290 circulates passively through the bloodstream. It reaches injured tissue and docks at the Innate Repair Receptor (IRR) — the EPOR + CD131 heterodimer — which is upregulated at sites of injury, inflammation, and metabolic stress (see “The targeting trick” below). At healthy tissue, the molecule largely passes by.
Intracellular cascade
Docking at the IRR fires a downstream signaling cascade: STAT3 → PI3K → Akt
- STAT3: anti-apoptotic gene expression (“keep this cell alive”)
- Akt: specifically disables the cell’s apoptosis program. A metabolically stressed cell hovering near programmed self-destruction — the Akt signal essentially pulls the trigger finger off the button. ARA-290 doesn’t heal; it stops the dying long enough for real repair to catch up.
- Amplification: one docking event activates hundreds of downstream proteins. The signal is amplified and runs long after the peptide itself has cleared.
Macrophage polarization
ARA-290 shifts macrophages from M1 mode (pro-inflammatory, demolition) to M2 mode (pro-repair, construction). This is why repeated dosing over days changes the whole tissue environment — not one big event, but a sustained shift in the immune tone of the injury site.
The targeting trick — how a “blind” molecule finds the wound
ARA-290 does not navigate. It has no homing machinery. It passively follows the bloodstream, which goes everywhere. The selectivity comes from two filters that stack at the injury site:
Filter 1 — Receptor upregulation. Inflammation, metabolic stress, and tissue damage cause cells to put more IRRs on their surface. Healthy tissue has few IRRs — the peptide floats past with almost nothing to grab. An injured cell has thrown up hundreds of IRRs. The peptide docks, the cascade fires.
Filter 2 — Downstream priming. Even if a healthy cell has some IRRs, the intracellular wiring isn’t primed for the cascade. The signal lands at low volume. At the injury site, the cell is already in metabolic stress and receptive — same molecular event, far louder response. Striking a match in an empty room vs. a room stacked with dry kindling. Same spark, completely different outcome.
Stack both: the molecule is blind, but the wound puts up the locks — and when the molecule floats through, it finds them.
Signaling pharmacology (why the short half-life is not a problem)
ARA-290 is cleared from the blood in under an hour. People who see that and conclude “it can’t work” are thinking in the wrong pharmacological framework.
Occupancy pharmacology (ibuprofen, most common drugs): the drug must physically sit on the target the whole time it’s working. Blood levels fall, effect falls. The effect tracks the drug concentration minute by minute.
Signaling pharmacology (ARA-290): the peptide is the trigger, not the effect. Its only job is to reach the receptor, dock, and flip the switch. Once it fires the STAT3/PI3K/Akt cascade, the biology carries the ball. Gene expression changes. Protein synthesis shifts. The machinery runs for days after the peptide is gone.
Think of it as a light switch: your finger touches it for half a second, the lights stay on for hours. ARA-290 is the finger. The cascade is the lights.
This is why the trial outcomes — meaningful pain reduction at weeks 4–8, objective nerve fiber improvement, sustained metabolic changes past the treatment window — are biologically expected, not surprising.
Pharmacokinetics
- Route: Subcutaneous injection — subcutaneous depot acts as a slow reservoir, avoiding the sharp spike of an IV push
- Peak blood levels: ~15–30 minutes post-injection
- Blood half-life: under 1 hour — 11 amino acids with no large protective structure; kidneys filter it rapidly
- Compare to: antibody drugs that linger for weeks; large proteins with half-lives of days. ARA-290 is here and gone — the effect, as described above, is not.
What the research shows
Brines 2015 — the cornerstone published RCT
PMID 25387363, PMC4365069. ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes. Brines M, Dunne AN, van Velzen M, et al. Mol Med 2015.
- Design: double-blind, placebo-controlled Phase 2; Netherlands Trial Register NTR3858; investigator-initiated
- Population: n=48 (24 ARA-290 / 24 placebo); Type 2 diabetics with neuropathic symptoms
- Dose: 4 mg SubQ self-injection daily × 28 days; 28-day observation period after
| Endpoint | ARA-290 | Placebo | Result |
|---|---|---|---|
| HbA1c at day 28 | −0.16% | −0.01% | p=0.002 |
| HbA1c at day 56 | −0.21% | +0.21% | continued improvement vs. reversal |
| Cholesterol/HDL ratio | reduced | — | p=0.039 |
| Triglycerides | decreased | — | p=0.043 |
| PainDetect score at day 28 | −3.3 pts | −1.1 pts | significant |
| PainDetect score at day 56 | −4.2 pts | −0.74 pts | p=0.037 |
| PainDetect tingling | improved | — | p=0.01 |
| PainDetect allodynia | improved | — | p=0.04 |
| Corneal nerve fiber density (subgroup) | +2.6 ± 1.0 fibers/mm² | +0.7 ± 1.3 (ns) | p=0.02 |
| RAND-36 vitality | improved | — | p=0.02 |
| RAND-36 physical role functioning | improved | — | p=0.05 |
Two results that stand out mechanistically:
- PainDetect improvement tracked with CNFD increase in the ARA-290 group but not placebo. Mechanistic + clinical congruence: the nerve regeneration explains the symptom improvement, not just a placebo response.
- No anti-drug antibodies at day 28. No immunogenicity signal — important safety-of-repeated-dosing data.
Conflict-of-interest disclosure (from paper): Brines, Dunne, and Cerami are officers of Araim Pharmaceuticals and hold equity. Funding included Dutch government grant NIRM FES0908, Swedish Research Council ALF, and Swedish Diabetes Association — mixed industry + government-funding profile, disclosed transparently in the paper.
Sarcoidosis SFN trial
Double-blind, 4 mg ARA-290 SubQ daily × 28 days in sarcoidosis-associated small-fiber neuropathy. SFNSL (Small Fiber Neuropathy Symptoms List) score decreased 9.1 ± 8.5 points, with increased small-nerve-fiber density on skin biopsy. This trial is the basis for ARA-290’s FDA Orphan Drug Designation for neuropathic pain in sarcoidosis.
Timeline of clinical effect (from trials + mechanism)
| Phase | Timeframe | What’s happening |
|---|---|---|
| Trigger | Minutes | IRR docking → STAT3/PI3K/Akt cascade fires |
| Clearance | <1 hour | Peptide gone; cascade runs independently |
| Cytokine shift | Hours | Early anti-inflammatory markers shift |
| Macrophage polarization | Days (repeated dosing) | M1→M2 consolidation; background fatigue may ease |
| Structural nerve repair | Weeks | Small nerve fiber regrowth; real pain score separation from placebo at weeks 4–8; laser evoked potentials trend the right way |
This is the shape of ARA-290’s clinical signature: minimal detectable change in week 1, meaningful separation from placebo at weeks 4–8. Small nerve fibers don’t regrow in a day. The trials’ primary endpoints were designed around this slow-repair biology.
Other studied contexts (preclinical)
- Diet-induced insulin resistance
- Diabetic retinopathy
- Diabetic autonomic neuropathy (Akita mice)
- Myocardial infarction and chronic heart failure
- Traumatic brain injury
- Burns and shock-induced multi-organ failure
Safety — the honest read
Brines 2015 adverse events (n=48 trial):
- ARA-290 arm (n=24): 54 mild + 9 moderate + 1 severe + 4 serious adverse events (SAEs)
- Placebo arm (n=24): 61 mild + 5 moderate
The four SAEs in the ARA-290 arm (transparent reporting):
- Renal insufficiency — patient on furosemide with borderline baseline renal function; creatinine rose from 119 → 159 μmol/L after week 2; adjudicated “possibly related”; renal function did not improve after ARA-290 was stopped while furosemide continued. Clinical note: patients with borderline renal function on loop diuretics merit monitoring.
- Cellulitis + fatal MI — 70-year-old male developed severe lower-extremity cellulitis ~2 weeks after his last dose and suffered a fatal myocardial infarction; adjudicated “unrelated” to ARA-290. 3–4. Two additional SAEs adjudicated “unlikely associated.”
The fatal MI in a 70-year-old — even adjudicated unrelated — is reported here because OHM’s editorial credibility is its transparency. The molecule did Phase 2 trials, the trial had four SAEs in a 24-person arm, and the data is published in full with explicit investigator adjudication. That’s the honest record.
Other safety findings:
- No clinically significant hematology or chemistry changes vs. baseline (confirming non-erythropoietic profile)
- No immunogenicity signal at 28 days
- No long-term multi-year safety data exists
Real-world protocol
The doses and schedules here are for educational and informational purposes only. These peptides are sold for research use only and are not FDA-approved drugs. This is not medical advice. Consult a qualified physician before beginning any protocol.
Trial-validated dose:
- 4 mg SubQ injection daily × 28 days — the dose from both Brines 2015 (T2D neuropathy) and the sarcoidosis SFN trial
- Reconstitution example: 4 mg vial + 1 mL bacteriostatic water = 4 mg/mL; a 4 mg dose = 1 mL = 100 units on a U-100 insulin syringe (a full syringe)
Community / anti-aging dosing (not formally validated):
- 0.5–1 mg SubQ daily, or 1–2 mg every other day
- Well below the trial dose; used in the biohacker community as a “longevity / nerve maintenance” pattern
- No published data validates this range — it’s extrapolation from the trial dose and general peptide community practice
Storage: refrigerated lyophilized; reconstitute with bacteriostatic water; ~30 days post-reconstitution
Cycle: 28-day blocks are the trial-validated pattern. Extended dosing past 28 days lacks published data. The slow-repair timeline (weeks 4–8 for meaningful symptom change) means a 28-day course starts showing benefits near its own end — a longer block or repeated cycles is the logical extension for chronic neuropathic conditions, but it’s not formally studied.
Regulatory status
- FDA Orphan Drug Designation for neuropathic pain in sarcoidosis — granted; meaningful regulatory advance. The FDA reviewed the data and acknowledged real potential benefit for a serious rare disease. Opens fast-track development pathways.
- Full FDA approval: never submitted. Development program never reached Phase 3.
- Araim Pharmaceuticals: closed as of 2026. Not a clinical failure — a financing failure. A small biotech couldn’t fund Phase 3 for niche indications; peptides are expensive to manufacture. Economics ended the company; the biology didn’t fail. The Brines/Cerami dual-receptor discovery and the published Phase 2 data remain in the scientific record regardless of the company’s fate.
- Post-closure status: patents may be expired; the molecule could be picked up by another developer. Orphan Drug precedents for molecule recovery exist.
- WADA: non-erythropoietic by design — cannot raise red blood cell count; sidesteps EPO prohibition entirely
Where experts disagree
Dosing at the community low end: the trial-validated dose is 4 mg/day × 28 days. The biohacker community uses 0.5–1 mg/day continuous as a maintenance or longevity pattern. There’s no published data on the low end; it’s extrapolation. The trial dose is what was actually tested. OHM’s position: present both honestly — the validated trial dose with its outcomes, and the community practice with its label.
“Did it fail?” The molecule produced statistically significant results on hard endpoints (HbA1c, PainDetect, corneal nerve fiber density). The company that held it ran out of money before full approval. These are two different things and the distinction matters: “failed Phase 2” vs. “passed Phase 2, company folded” carry very different weight when assessing the molecule’s potential.
Duration of benefit after the 28-day course: the trial has a 28-day observation period post-treatment; HbA1c continued improving in that window (−0.21% at day 56 vs. +0.21% in placebo). What happens at day 90, day 180 is unknown. The cascade-based signaling model predicts durable benefit, but the human data doesn’t reach that far.
Where this sits in the OHM endogenous-protection map
| Peptide | Origin | Primary role | Catalog status |
|---|---|---|---|
| ARA-290 | Engineered from EPO helix-B face | Peripheral nerve repair + anti-inflammation via IRR | US Pure Peptides (OHM20) |
| Humanin | Mitochondrial-derived (MT-RNR2 gene) | CNS neuroprotection + longevity + IGF-1 axis | Not in catalog — roadmap |
| MOTS-c | Mitochondrial-derived (MT-RNR2 gene) | Metabolic / insulin sensitivity | In Alyve catalog (OHM-15) |
| SS-31 (Elamipretide) | Mitochondrial-targeted synthetic | Mitochondrial ROS scavenging; FDA-approved for Barth syndrome | US Pure Peptides (OHM20) |
Commercial layer
ARA-290 is available from US Pure Peptides — use code OHM20 for 20% off.
- ISO 17025-accredited third-party COA testing on every batch
- HPLC + Mass Spec verified; free bacteriostatic water with every order
- Same-day dispatch before 2pm EST; free shipping on orders over $200
- 30% commission to OHM — the preferred non-Alyve routing
BioLongevity Labs (OHM-15, 15% off) is the tertiary fallback.
ARA-290 is not in Alyve’s current launch catalog. Route all ARA-290 buyers to US Pure Peptides first.
Why ARA-290 stands out commercially: it has a published placebo-controlled Phase 2 RCT with significant endpoints, FDA Orphan Drug Designation, and a completely non-erythropoietic profile (no red-blood-cell concerns, no EPO regulatory baggage). For the T2D and neuropathy customer cluster — which overlaps with the Retatrutide GLP-1 audience — this is a high-credibility addition. A customer running Reta for metabolic health who also has peripheral neuropathy is an ARA-290 natural.
Sources
- original research synthesis; source of the Brines 2015 RCT data, safety detail, protocol
- “Fable LLM from Anthropic” (Free Knowledge channel); July 2026; source of the signaling pharmacology framework, two-filter targeting mechanism, timeline systematization, Araim closure 2026 confirmation
- Brines et al. 2015 Mol Med, PMID 25387363, PMC4365069 — the cornerstone ARA-290 Phase 2 trial; fully verified
queue: (1) for the Brines/Cerami dual-receptor mechanism paper (pre-2015, separate from the RCT); (2) for the sarcoidosis SFN trial (Orphan Drug basis); (3) current FDA Orphan Drug Designation status (active/lapsed post-Araim closure); (4) WADA prohibited-list current status; (5) ARA-290 molecular formula and sequence (PubChem CID for cibinetide).
Related: Humanin & ARA-290 — the endogenous protection cluster · MOTS-c · SS-31 (Elamipretide) · BPC-157 · Retatrutide · atherosclerosis-cardiovascular.
Sources & references
- original research synthesis; source of the Brines 2015 RCT data, safety detail, protocol
- “Fable LLM from Anthropic” (Free Knowledge channel); July 2026; source of the signaling pharmacology framework, two-filter targeting mechanism, timeline systematization, Araim closure 2026 confirmation
- Brines et al. 2015 Mol Med, PMID 25387363, PMC4365069 — the cornerstone ARA-290 Phase 2 trial; fully verified
queue: (1) for the Brines/Cerami dual-receptor mechanism paper (pre-2015, separate from the RCT); (2) for the sarcoidosis SFN trial (Orphan Drug basis); (3) current FDA Orphan Drug Designation status (active/lapsed post-Araim closure); (4) WADA prohibited-list current status; (5) ARA-290 molecular formula and sequence (PubChem CID for cibinetide).
Related: Humanin & ARA-290 — the endogenous protection cluster · MOTS-c · SS-31 (Elamipretide) · BPC-157 · Retatrutide · atherosclerosis-cardiovascular.