ARA-290 Research Guide — EPO-Derived Innate Repair Receptor Peptide, Non-Hematopoietic Tissue Protection & Neuropathy Biology (2026)
- ARA-290 (also written ARA 290; also designated pyroglutamate helix B surface peptide) is a synthetic 11-amino acid peptide (sequence: Pyr-Glu-Glu-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser-OH; MW ~1,257 Da) engineered from the helix B surface region of erythropoietin (EPO). It was developed by Araim compound (Michael Brines and Anthony Cerami) to separate EPO’s tissue-protective, anti-inflammatory, and neuroprotective activities from its hematopoietic (erythropoiesis-stimulating) effects. YPB offers research-grade ARA-290 as YPB catalog (Research Use Only).
- Mechanism: ARA-290 selectively activates the innate repair receptor (IRR) — a heteromeric receptor complex consisting of the erythropoietin receptor (EPOR) and the beta-common receptor (βcR; CD131). The IRR is structurally and functionally distinct from the homodimeric EPOR (EPOR²) that drives erythropoiesis. IRR is selectively upregulated in injured, inflamed, or metabolically stressed tissue and is largely absent in healthy uninjured cells. ARA-290 binding to IRR activates anti-apoptotic, anti-inflammatory, and cytoprotective intracellular signaling (PI3K/Akt, NF-κB suppression, ERK1/2) without engaging EPOR² — therefore producing no erythropoiesis, no increased hematocrit, and no thrombotic risk.
- Clinical evidence: Sarcoidosis-associated small fiber neuropathy (SFN) RCT: ARA-290 reduced allodynia and improved autonomic function in a randomized, double-blind pilot study. T2DM neuropathy Phase 2 (Brines et al. 2014; PMC4365069): improved metabolic control and neuropathic symptoms; 23% increase in corneal nerve fiber area at 4 mg/day for 28 days. FDA orphan compound designation granted for neuropathic pain in sarcoidosis.
- Critical distinction from EPO: Full erythropoietin (rhEPO) activates both EPOR² (hematopoiesis; erythrocytosis; thrombosis risk) and IRR (tissue protection). ARA-290 activates only IRR. This decoupling is the entire pharmacological rationale for ARA-290 as a research tool and potential therapeutic — it provides EPO’s protective biology without EPO’s dangerous hematological effects. Not research-grade for any indication beyond orphan designation. Research Use Only (RUO). Updated April 2026.
What Is ARA-290 and Why Does the EPO/Non-Hematopoietic Distinction Matter?
No Erythropoiesis Activity
FDA Orphan compound (Sarcoidosis SFN)
ARA-290 was designed to answer a question that emerged from EPO research in the late 1990s: erythropoietin, long known exclusively as the hormone that stimulates red blood cell production, was found to have potent tissue-protective, anti-inflammatory, and neuroprotective effects in pre-clinical models that were entirely independent of its hematopoietic activity. Updated April 2026. The problem was that using full EPO for these protective effects carried serious risks — erythropoiesis-stimulating agents increase red blood cell counts and hematocrit, increasing thrombosis risk and causing cardiovascular events, particularly in high-dose settings. Multiple clinical trials of EPO for neuroprotection were terminated or produced net harm due to thrombotic complications at doses required for the protective effect.
Michael Brines and Anthony Cerami identified the molecular basis of this bifunctionality: EPO’s hematopoietic activity is mediated through the homodimeric EPOR² receptor complex; EPO’s tissue-protective activity is mediated through a distinct heteromeric receptor complex (EPOR + βcR) designated the innate repair receptor (IRR). These two receptor systems are structurally and pharmacologically separable: EPO activates both; properly designed peptide fragments of EPO can selectively activate one. ARA-290 was engineered from the helix B surface region of EPO — the surface of the EPO molecule that interfaces with the IRR but not with the EPOR² hematopoietic receptor — to create an IRR-selective, non-hematopoietic tissue-protection peptide.
Key Characteristics
| Parameter | Value |
|---|---|
| Full Name | ARA-290; ARA 290; pyroglutamate helix B surface peptide |
| Sequence | Pyr-Glu-Glu-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser-OH (11 amino acids; N-terminus is pyroglutamate — cyclic form of glutamic acid) |
| Molecular Weight | ~1,257 Da |
| Developer | Araim compound (Michael Brines, Anthony Cerami); EPO helix B surface engineering |
| Receptor Target | Innate repair receptor (IRR) = heteromeric complex of EPOR (erythropoietin receptor) + βcR (beta-common receptor; CD131; also shared by IL-3, IL-5, GM-CSF) |
| IRR vs. EPOR² distinction | IRR (EPOR + βcR): tissue-protective, anti-inflammatory, anti-apoptotic; selectively upregulated in injured/inflamed tissue. EPOR² (EPOR homodimer): drives erythropoiesis in bone marrow. ARA-290 activates IRR only; does NOT activate EPOR². |
| Downstream Signaling (IRR) | PI3K/Akt (anti-apoptotic); ERK1/2 (cytoprotective); NF-κB suppression (anti-inflammatory); TNF antagonism; reduced pro-inflammatory cytokine production |
| Hematopoietic Activity | None — does not stimulate erythropoiesis, does not increase hematocrit, no thrombosis risk from red blood cell mass increase |
| Clinical Context | SFN sarcoidosis RCT: reduced allodynia, improved autonomic function; T2DM neuropathy Phase 2 (Brines 2014): improved metabolic control and neuropathic symptoms; 23% corneal nerve fiber area increase; FDA orphan compound designation (sarcoidosis neuropathic pain) |
| FDA Status | Orphan compound designation granted for neuropathic pain in sarcoidosis; not research-grade for any indication. Research Use Only (RUO). |
| WADA Status | Not listed on WADA Prohibited List 2025 (no hematopoietic activity; IRR-selective) |
| Half-Life | Short (11-AA peptide; rapid plasma clearance); research protocols use daily or multi-day administration; no extended release modification |
| Storage | Lyophilized: −20°C. Reconstituted in sterile water or PBS; 2–8°C, use within 14 days. Pyroglutamate N-terminus is stable under standard conditions. |
How Does ARA-290 Work? The Innate Repair Receptor System
EPO’s Bifunctionality: Two Separate Receptor Systems
Erythropoietin (EPO) is produced primarily by the kidney in response to hypoxia and drives red blood cell production by activating the EPOR homodimer (EPOR²) on erythroid progenitor cells in bone marrow. This is EPO’s canonical hematopoietic function. Beginning in the 1990s, Brines, Cerami, and colleagues discovered that EPO also has potent tissue-protective effects in brain, heart, kidney, and peripheral nerve tissue — reducing ischemia-reperfusion injury, suppressing inflammation, and protecting neurons from apoptosis. The critical finding was that this tissue-protective EPO activity was mediated through a different receptor complex: the EPOR + βcR heterodimer, designated the innate repair receptor (IRR). The βcR (CD131) is the beta chain shared by multiple cytokine receptors (IL-3R, IL-5R, GM-CSFR); its heterodimerization with EPOR creates a receptor with entirely different downstream signaling properties from EPOR².
IRR Tissue Selectivity: Injury-Upregulated Expression
A key property of the IRR that makes ARA-290 pharmacologically attractive is its injury-selective expression. The βcR/CD131 component of IRR is upregulated in damaged, inflamed, or metabolically stressed tissue, while being expressed at low levels in healthy uninjured cells. This means IRR-targeted compounds like ARA-290 are preferentially active at sites of injury and inflammation — a built-in tissue selectivity that could reduce off-target effects. In sarcoidosis (a granulomatous inflammatory disease that damages small nerve fibers) and in diabetic neuropathy (where metabolic stress drives chronic nerve damage), the IRR is activated in the relevant pathological tissue, providing the mechanistic rationale for ARA-290’s observed clinical activity in these specific conditions.
IRR Downstream Signaling: Anti-Apoptotic and Anti-Inflammatory
IRR activation by ARA-290 drives intracellular signals that collectively protect tissue from injury-related cell death and suppress inflammatory amplification: PI3K/Akt activation provides anti-apoptotic signaling that counteracts caspase cascade activation; ERK1/2 activation supports cell survival; NF-κB pathway suppression reduces pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6); direct antagonism of TNF-mediated inflammatory signaling; and activation of anti-oxidant pathways that reduce reactive oxygen species-mediated cellular damage. In neural tissue, these signals collectively support axon preservation, reduce inflammatory neuropathy, and promote regeneration of damaged small fiber nerves.
What Research Applications Has ARA-290 Been Studied For?
Small Fiber Neuropathy (SFN) Research
ARA-290’s most clinically developed application is sarcoidosis-associated small fiber neuropathy, a condition where granulomatous inflammation damages the unmyelinated C-fiber and thinly myelinated Aδ-fiber peripheral nerve fibers responsible for pain, temperature, and autonomic sensation. A randomized, double-blind pilot study in sarcoidosis SFN research subjects demonstrated that ARA-290 reduced allodynia (pain from non-painful stimuli) and improved autonomic function endpoints, including skin vasomotor reflexes. This study, combined with supporting preclinical data, led to FDA orphan compound designation for neuropathic pain in sarcoidosis.
Diabetic Neuropathy Research
Brines et al. (2014, PMC4365069) published Phase 2 data for ARA-290 in type 2 diabetes research subjects with painful neuropathy: over 28 days of 4 mg/day SC administration, the study documented improved neuropathic symptom scores, improved metabolic control markers, and a 23% increase in corneal nerve fiber area (measured by confocal microscopy — the gold-standard in vivo assessment of small fiber nerve density). Corneal nerve fiber density is a validated surrogate for systemic small fiber neuropathy severity; an increase indicates actual nerve fiber regeneration or preservation rather than merely symptomatic improvement.
Ischemia-Reperfusion and Organ Protection Research
Preclinical data across multiple organ systems (brain, kidney, heart) demonstrate ARA-290 protection against ischemia-reperfusion injury through IRR-mediated PI3K/Akt and NF-κB suppression. These studies use ARA-290 as a tool to isolate the IRR-mediated component of EPO’s organ-protective effects from the confound of erythropoiesis-related changes in oxygen delivery that complicate full EPO research designs.
Neurotoxicity Protection Research
Published preclinical data (PMC11831023) examined ARA-290’s neuroprotective effects against cadmium-induced toxicity in PC12 neuronal cells, demonstrating improved cell viability, reduced DNA damage, and reduced apoptosis markers — consistent with the PI3K/Akt anti-apoptotic and antioxidant signaling mechanisms.
What Does the Clinical Data Show?
| Trial / Context | Design | Key Finding & Adverse Events | Year |
|---|---|---|---|
| Sarcoidosis SFN — RCT pilot | Randomized, double-blind, placebo-controlled / sarcoidosis research subjects with SFN symptoms | ARA-290 reduced allodynia; improved autonomic function endpoints (skin vasomotor reflexes). No safety concerns from clinical or laboratory assessments; well tolerated. Led to FDA orphan compound designation for neuropathic pain in sarcoidosis. (Mol Med, 2013) | 2013 |
| T2DM neuropathy — Phase 2 | Phase 2 / T2DM subjects with painful neuropathy / 4 mg/day SC × 28 days | Improved neuropathic symptom scores; improved metabolic control markers; 23% increase in corneal nerve fiber area (validated objective neuropathy endpoint by confocal microscopy). No serious adverse events; well tolerated. (Brines et al. 2014, PMC4365069) | 2014 |
| Single/multiple ascending dose safety studies | Healthy volunteers and kidney disease research subjects | ARA-290 well tolerated; no erythropoietic activity (hematocrit unchanged); no hematological or thrombotic adverse events consistent with absence of EPOR² activation. Established favorable safety profile for no-hematopoietic IRR-selective dosing. | Various |
| Preclinical ischemia-reperfusion models | In vivo (brain, heart, kidney; multiple species) | ARA-290 reduced infarct size, improved organ function in ischemia-reperfusion models; PI3K/Akt anti-apoptotic mechanism confirmed; no erythropoietic confound. Well tolerated across multiple organ protection models. | Multiple |
How Does ARA-290 Compare to Other Neuroprotection Research Compounds?
| Parameter | ARA-290 | Semax | Selank | BPC-157 |
|---|---|---|---|---|
| Primary Mechanism | IRR (EPOR + βcR) activation: anti-apoptotic, anti-inflammatory, cytoprotective; injury-selective receptor expression | ACTH analog; BDNF/NGF upregulation; dopaminergic; cognitive enhancement via neurotrophic factor induction | Tuftsin analog; anxiolytic; BDNF upregulation; GABAergic modulation; immune-brain axis | VEGF/EGF upregulation; angiogenesis; tissue repair; NO system; FAK-paxillin pathway |
| Target System | Type I cytokine receptor (EPOR/βcR heterodimer); injury-upregulated expression | Melanocortin axis (ACTH/MC4R); CNS neurotrophic | Immune-brain peptide; GABAergic, serotonergic, tryptophan metabolism | Wound repair, angiogenesis; multiple growth factor pathways |
| Clinical Evidence | RCT (sarcoidosis SFN); Phase 2 (T2DM neuropathy); FDA orphan designation; corneal nerve fiber regeneration data | Russian wellness support; ACTH analog literature; no FDA approval | Russian wellness support; anxiety/cognition literature; no FDA approval | Phase 2 gastric ulcer (BPC-157 related); preclinical across multiple models |
| Hematopoietic Activity | None — IRR-selective; no EPO receptor homodimer activation; no erythrocytosis | N/A (CNS mechanism) | N/A (immune/CNS mechanism) | N/A (tissue repair mechanism) |
| Primary Research Application | Neuropathy models; ischemia-reperfusion organ protection; IRR pathway biology; inflammation-injury research | Cognitive biology; BDNF pathway; stroke recovery models | Anxiety/stress biology; immune-brain axis; GABAergic research | Tissue repair; angiogenesis; tendon/ligament; GI healing |
| YPB SKU | YPB catalog (RUO) | YPB.221 — see guide | YPB.214 — see guide | YPB.201 — see guide |
ARA-290 is distinct from other neuroprotection peptides in the YPB catalog because it targets an injury-selective receptor system (IRR) derived from EPO’s tissue-protection domain rather than classic neurotrophic or neuropeptide pathways. Semax (see the Semax Research Guide) and Selank (see the Selank Research Guide) operate through ACTH/MC4R and tuftsin/GABAergic mechanisms respectively — mechanistically non-overlapping with IRR biology. Together they cover the neuroinflammation-protection (ARA-290/IRR), cognitive-neurotrophic (Semax/BDNF), and anxiolytic-immune (Selank) dimensions of neuroprotection research.
What Should Researchers Know About ARA-290 Stability and Handling?
Pyroglutamate N-Terminus Stability
The pyroglutamate (Pyr-Glu) N-terminal residue in ARA-290 provides meaningful stability vs. a free N-terminal glutamic acid: aminopeptidases do not efficiently recognize cyclic pyroglutamate as a substrate, extending the effective N-terminal protection. Standard storage precautions apply. Lyophilized material is stable at −20°C for up to 24 months; reconstituted solution at 2–8°C for up to 14 days.
COA Verification
HPLC purity (≥98%) and MS confirmation at ~1,257 Da. The pyroglutamate N-terminus should be confirmed by the correct molecular weight (free N-terminal Glu-Glu would show ~1,275 Da; pyroglutamate N-terminal Pyr-Glu-Glu shows ~1,257 Da — the −18 Da difference reflects the loss of water during cyclization). N-terminal sequencing confirming pyroglutamate (vs. free glutamic acid) is the definitive structural quality parameter. All YPB ARA-290 batches include lot-traceable COA documentation through the COA Library.
Key Research Findings
- IRR-selective EPO analog: Activates EPOR/βcR (IRR) without engaging EPOR² (hematopoietic); no erythropoiesis, no hematocrit increase, no thrombosis risk. Decouples EPO’s tissue-protective biology from its hematological effects.
- Injury-selective receptor (IRR): βcR/CD131 is upregulated in injured/inflamed tissue; IRR activation is therefore preferentially active at pathological sites.
- PI3K/Akt anti-apoptotic + NF-κB suppression: Two primary downstream pathways for tissue protection; also ERK1/2 cytoprotective signaling and TNF antagonism.
- Sarcoidosis SFN RCT: Reduced allodynia; improved autonomic function; well tolerated; FDA orphan compound designation for neuropathic pain in sarcoidosis.
- T2DM neuropathy Phase 2 (Brines 2014, PMC4365069): 23% corneal nerve fiber area increase; improved neuropathic symptoms and metabolic control at 4 mg/day × 28 days.
- Pyroglutamate N-terminus: Cyclic form of Glu; aminopeptidase resistance; confirms correct structure vs. free Glu N-terminus (1,257 Da vs. 1,275 Da by MS); naturally occurring motif in neuropeptides.
- 11-AA linear peptide: MW ~1,257 Da; short; water-soluble; standard peptide handling protocols apply; no DMSO required.
- Not research-grade beyond orphan designation: Orphan compound designation ≠ approval; ARA-290 is not an approved compound for any indication. Research Use Only.
Browse the Full Research Catalog
Market Demand and Research Interest
| Demand Indicator | ARA-290 Data Point |
|---|---|
| Clinical milestone | FDA orphan compound designation for neuropathic pain in sarcoidosis; Phase 2 T2DM neuropathy data (2014) |
| Unique mechanism | Only IRR-selective EPO-derived peptide in YPB catalog; only compound targeting the EPOR/βcR heteromeric receptor system; injury-selective tissue protection |
| Research applications | Neuropathy biology; ischemia-reperfusion organ protection; IRR signaling pathway; EPO tissue-protection decoupling from hematopoiesis |
| Araim compound | Developer Araim (Brines/Cerami) continues IRR-based research; ongoing publications on ARA-290 and next-generation IRR agonists |
| Corneal nerve fiber data | 23% area increase — among the most convincing structural neuroprotection endpoints published for any research peptide; objective confocal microscopy measurement |
| Keyword difficulty range | Very low (KD <5) |
How Can Researchers Offer ARA-290 Under Their Own Brand?
Wholesale Pricing & Margin Analysis
| SKU | Compound | Premier ($497/mo) | Core ($297/mo) | Suggested MSRP | Premier Margin |
|---|---|---|---|---|---|
| YPB Catalog (RUO) | ARA-290 (Pyroglutamate Helix B Surface Peptide) | TBC Premier | TBC Core | TBC | TBC at Premier tier |
Contact the YPB team for confirmed SKU, configuration, Premier and Core tier pricing. Use the YPB Profit Calculator to model projected revenue. White-label brands offering ARA-290 alongside Semax and Selank create a comprehensive neuroprotection research catalog covering three non-overlapping mechanisms: IRR injury-selective cytoprotection (ARA-290), ACTH/BDNF neurotrophic (Semax), and anxiolytic/immune-modulating (Selank) — from a single neuroprotection research buyer audience. Download the full catalog for all neuroprotection category pricing.
Methodology & Data Sources
Methodology & Data Sources
Scientific literature: PubMed searched for “ARA-290,” “ARA 290,” “innate repair receptor,” “pyroglutamate helix B EPO,” and “non-hematopoietic EPO neuropathy.” Search conducted through April 2026.
Key sources: Brines et al. (2014) PMC4365069 (T2DM neuropathy Phase 2, 23% corneal nerve fiber increase); Sarcoidosis SFN RCT (Mol Med, 2013); Brines & Cerami (2008) J Intern Med (EPO tissue protection mechanisms); Brines & Cerami (2012) Mol Med (IRR receptor characterization); PMC5741312 (neuropathy IRR review); PMC11831023 (cadmium neurotoxicity protection).
Limitations: ARA-290 has published Phase 2 clinical data but is not research-grade for any indication (orphan compound designation ≠ approval). Clinical data from sarcoidosis and T2DM neuropathy studies are from small-N trials; larger confirmatory studies would be needed for approval. The IRR receptor system and the specific molecular pharmacology of ARA-290 IRR engagement were characterized primarily by the Araim compound research group (Brines/Cerami); independent replication of the full receptor mechanism is developing but not yet as extensive as the published trial data. This article is for educational purposes only.
References
- Brines, M., Dunne, A. N., van Velzen, M., Proto, P. L., Ostenson, C. G., Kirk, R. I., Petropoulos, I. N., Javed, S., Malik, R. A., Cerami, A., & Dahan, A. (2014). ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in research subjects with type 2 diabetes. Mol Med, 20, 658–666. PMC4365069
- Brines, M., & Cerami, A. (2008). Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response. J Intern Med, 264(4), 405–432. (PMID: 18676614; IRR and EPO tissue protection foundational review.)
- Brines, M., & Cerami, A. (2012). The receptor that tames the innate immune response. Mol Med, 18, 486–496. (IRR receptor characterization and ARA-290 mechanism.)
- van Velzen, M., Heij, L., Niesters, M., Cerami, A., Dunne, A., Dahan, A., & Brines, M. (2014). ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opin Investig compounds, 23(4), 541–550. (Sarcoidosis SFN clinical context.)
- Sarcoidosis SFN pilot RCT. (2013). Safety and efficacy of ARA 290 in sarcoidosis research subjects with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med. PMC3563705.
- Neuropathy IRR review. (2017). Targeting the innate repair receptor to treat neuropathy. PMC5741312. (Comprehensive IRR neuropathy context; ARA-290 clinical summary.)
- Brines, M., Grasso, G., Fiordaliso, F., Sfacteria, A., Ghezzi, P., Fratelli, M., Latini, R., Xie, Q. W., Smart, J., Su-Rick, C. J., Pobre, E., Diaz, D., Gomez, D., Hand, C., Coleman, T., & Cerami, A. (2004). Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci USA, 101(41), 14907–14912. (EPOR/βcR IRR heteromer original characterization.)
- Schmidt, R. E., et al. (2011). Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia. Exp Neurol, 232(1), 126–135. (Diabetic neuropathy preclinical ARA-290 data.)
- ARA290 cadmium neurotoxicity. (2025). Mechanisms of ARA290 in counteracting cadmium-triggered neurotoxicity in PC12 cells. PMC11831023. (PI3K/Akt neuroprotection mechanism.)
Frequently Asked Questions
ARA-290 (pyroglutamate helix B surface peptide; Pyr-Glu-Glu-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser-OH; MW ~1,257 Da; 11 AA) is a synthetic peptide engineered from the helix B surface region of erythropoietin (EPO) to selectively activate the innate repair receptor (IRR) — a heteromeric complex of EPOR + βcR (CD131) — without activating the hematopoietic EPOR homodimer (EPOR²). In research models, IRR activation drives anti-apoptotic (PI3K/Akt), anti-inflammatory (NF-κB suppression, TNF antagonism), and cytoprotective (ERK1/2) signaling in injured/inflamed tissue. IRR is selectively upregulated at sites of injury; ARA-290 is therefore preferentially active in pathological tissue contexts. Clinical data: sarcoidosis SFN RCT (reduced allodynia, improved autonomic function; FDA orphan designation); T2DM neuropathy Phase 2 (Brines 2014, PMC4365069): 23% corneal nerve fiber area increase; improved neuropathic symptoms at 4 mg/day × 28 days; no erythropoietic activity. Not research-grade. Research Use Only (RUO). Updated April 2026.
Erythropoietin’s hematopoietic activity is mediated through the EPOR homodimer (EPOR²) expressed on erythroid progenitor cells in bone marrow. EPO binding to EPOR² activates JAK2/STAT5 signaling that drives red blood cell differentiation and proliferation. ARA-290 was designed from the helix B surface region of EPO — specifically the molecular surface that contacts the tissue-protective innate repair receptor (EPOR + βcR), rather than the surface that contacts EPOR² for erythropoiesis. The two receptor binding surfaces on EPO are structurally distinct: the helix A/helix C “site 1” and “site 2” interfaces contact EPOR²; the helix B surface contacts the EPOR/βcR IRR. By using only the helix B surface residues, ARA-290 engages IRR without the molecular features required for EPOR² homodimer engagement. In clinical studies (single/multiple ascending dose; kidney disease research subjects; T2DM research subjects), ARA-290 produced no change in hematocrit, hemoglobin, or reticulocyte count — confirming complete separation of IRR activity from hematopoietic EPOR² activity.
The innate repair receptor (IRR) is a heteromeric type I cytokine receptor complex consisting of EPOR (the erythropoietin receptor) paired with βcR (beta-common receptor; CD131). The βcR is also a shared component of the IL-3, IL-5, and GM-CSF receptor systems; in the context of IRR, its heterodimerization with EPOR creates a receptor with entirely different signaling properties from either EPOR² or the classical βcR cytokine receptors. The injury-selective expression pattern of IRR is primarily attributable to βcR/CD131 expression being upregulated in metabolically stressed, inflamed, or injured cells — including neurons, cardiomyocytes, endothelial cells, and macrophages — while being expressed at low levels in healthy uninjured tissue of the same cell types. This selective upregulation creates a situation where IRR-targeted compounds like ARA-290 are preferentially active where tissue damage is occurring, rather than systemically. This injury selectivity is part of the pharmacological rationale for ARA-290’s observed clinical activity specifically in neuropathy conditions where small fiber nerve damage is the pathological focus.
Corneal nerve fiber density (measured by confocal microscopy of the sub-basal plexus of the cornea) is a validated, non-invasive in vivo surrogate biomarker for systemic small fiber neuropathy. The cornea has the highest small nerve fiber density of any body surface and its nerve fibers are accessible to direct visualization without biopsy. In T2DM neuropathy, corneal nerve fiber density correlates with intraepidermal nerve fiber density in skin punch biopsies (the traditional SFN gold standard) and with neuropathic symptom severity. A 23% increase in corneal nerve fiber area after 28 days of ARA-290 in Brines et al. (2014) is significant for two reasons: first, it represents an objective structural endpoint rather than only symptomatic improvement, suggesting actual nerve fiber preservation or regeneration rather than just pain modification; second, the 23% magnitude is substantial for a 4-week treatment period — most neuroprotective interventions that show any corneal fiber benefit show much smaller changes. The finding positioned ARA-290 as a potential nerve-regenerative compound rather than only a symptomatic/compound with research interest in.
ARA-290, Semax, and Selank are all neuroprotection-relevant research peptides but address entirely different receptor systems and research questions. ARA-290 targets the innate repair receptor (EPOR/βcR) — a type I cytokine receptor system that is injury-upregulated and mediates anti-apoptotic, anti-inflammatory tissue protection specifically in damaged neural and other tissue. Its primary research question is: “How does the innate repair system protect tissue from injury-induced death and inflammation?” Semax (ACTH4–10 analog) primarily activates the melanocortin receptor system (MC4R) and upregulates BDNF, NGF, and neurotrophic pathways in the CNS, with cognitive enhancement and stroke recovery applications. Its primary research question is: “How do ACTH-derived peptides and neurotrophic factors support neural function and recovery?” Selank (tuftsin analog) modulates the GABAergic and serotonergic systems with anxiolytic and immune-modulating effects. Its primary research question is: “How does tuftsin-related peptide signaling affect anxiety, immune-brain axis, and cognitive performance?” All three address neuroprotection from non-overlapping pharmacological angles and serve complementary roles in a comprehensive neuroprotection research catalog.
Yes. YourPeptideBrand.com provides white-label dropship for ARA-290 (Research Use Only). White-label storefronts include pre-built RUO-compliant product pages with IRR mechanism descriptions, non-hematopoietic EPO biology context, clinical neuropathy data (FDA orphan designation; Phase 2 corneal nerve fiber data clearly framed as research context; well tolerated), and COA library links. Contact the YPB team for confirmed SKU, configuration, Premier and Core pricing, and use the profit calculator to model projected revenue.
Every ARA-290 batch includes a lot-specific COA: HPLC purity (≥98%), MS confirmation at ~1,257 Da (pyroglutamate Pyr-Glu N-terminus confirmed; free Glu N-terminal non-cyclized form would show ~1,275 Da — the −18 Da mass shift from cyclization is the critical structural confirmation), endotoxin (<1 EU/mg), TAMC, and TYMC. The ~1,257 Da (vs. 1,275 Da) MS confirmation is the most critical single quality parameter as it simultaneously confirms the pyroglutamate cyclization that provides aminopeptidase protection and the correct IRR-binding conformation derived from the EPO helix B surface geometry. All lots are traceable through the batch-specific COA library.
Position ARA-290 as the injury-repair neuroprotection tool: the EPO-derived peptide that provides EPO’s tissue-protective biology (anti-apoptotic, anti-inflammatory, nerve-regenerative) without EPO’s hematological effects (erythrocytosis, thrombosis risk). Key narrative points for catalog copy: (1) FDA orphan compound designation establishes regulatory credibility in the neuropathic pain/neuroprotection space; (2) the 23% corneal nerve fiber area increase is an objective structural regeneration endpoint that is more compelling than symptomatic pain scores alone; (3) “EPO’s tissue-protection without EPO’s hematological effects” is a uniquely communicable research rationale that no other catalog compound provides. The injury-selective IRR upregulation means ARA-290 is specifically relevant to researchers studying neuropathy, ischemia-reperfusion protection, and inflammatory tissue damage — three well-funded research areas with high demand for mechanistically specific research tools.
Key Takeaways
Research Takeaways
- IRR-selective (not EPOR²): EPOR/βcR heterodimer; injury-upregulated expression; anti-apoptotic/anti-inflammatory/cytoprotective; no erythropoiesis, no hematocrit increase, no thrombotic risk.
- PI3K/Akt + NF-κB suppression: Two primary downstream arms; ERK1/2 cytoprotective; TNF antagonism. Mechanism confirmed in multiple preclinical and clinical studies.
- Phase 2 T2DM neuropathy (Brines 2014, PMC4365069): 23% corneal nerve fiber area increase; improved symptoms; well tolerated at 4 mg/day × 28 days.
- Sarcoidosis SFN RCT: Reduced allodynia; improved autonomic function; FDA orphan compound designation for neuropathic pain in sarcoidosis.
- Pyroglutamate N-terminus: Cyclic Glu; aminopeptidase resistance; confirm by MS at 1,257 Da (not 1,275 Da for non-cyclized form).
- Not research-grade: Orphan designation only; no approved indication. Research Use Only.
- Injury-selective biology: IRR upregulated in damaged/inflamed tissue; ARA-290 preferentially active at pathological sites — built-in tissue selectivity.
Business Takeaways
- FDA orphan designation provides regulatory credibility for catalog positioning in neuropathic pain research.
- Unique EPO/non-hematopoietic story — no competing catalog compound shares this mechanism or narrative.
- ARA-290 + Semax + Selank neuroprotection trio covers IRR tissue protection, ACTH/BDNF neurotrophic, and anxiolytic/immune-brain from a single neuroprotection buyer audience.
- Contact YPB for confirmed SKU and pricing on ARA-290.
Ready to add ARA-290 to your research catalog? Book a consultation with the YPB team.
[ypb_studies peptide=”ara-290″]