Description
ARA-290 (Cibinetide) – Advanced Biochemical Mechanism & Signaling Profile
Erythropoietin-Derived Helix-B Peptide
ARA-290 is a synthetic 11–amino-acid peptide derived from the B-helix region of erythropoietin (EPO). Unlike full-length EPO, ARA-290 does not activate the classical EPO receptor homodimer involved in erythropoiesis.
Instead, research demonstrates selective binding to the Innate Repair Receptor (IRR), a heterodimer composed of:
-
EPO Receptor (EPOR) + CD131 (β-common receptor)
This selective activity allows study of cytoprotective and anti-inflammatory signaling independent of erythropoietic pathways.
✅ Primary Signaling Pathways
Binding of ARA-290 to the EPOR–CD131 IRR complex activates intracellular kinase signaling cascades:
1. JAK2/STAT3 Pathway
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IRR engagement → JAK2 phosphorylation
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JAK2 phosphorylates STAT3 and STAT5
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STATs translocate to the nucleus to regulate target genes
Gene targets studied:
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SOCS3 (feedback inhibitor of cytokine signaling)
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Bcl-xL (cell-survival protein)
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Heme oxygenase-1 (HO-1)
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Antioxidant response genes
2. PI3K/Akt Pathway
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PI3K activation → PIP3 generation
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Recruitment and phosphorylation of Akt (Ser473, Thr308)
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Akt influences mitochondrial survival signaling, apoptosis suppression, and metabolic regulation
Downstream influences:
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GSK-3β phosphorylation (inactivation)
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mTOR modulation (cellular stress & repair models)
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FOXO transcription factors
3. NF-κB Modulation
ARA-290 has been studied for suppression of:
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IKK activity
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NF-κB nuclear translocation
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Pro-inflammatory gene transcription
Genes negatively regulated in models:
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TNF-α
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IL-1β
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IL-6
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MCP-1 (CCL2)
✅ Enzymes & Molecular Targets
Research has examined effects on:
| Enzyme / Protein | Functional Outcome |
|---|---|
| JAK2 | IRR-dependent phosphorylation cascade |
| STAT3/5 | Nuclear transcription modulation |
| IKK Complex | Reduced NF-κB activation |
| Caspases | Downstream apoptosis-related proteins |
| COX-2 / iNOS | Often reduced in inflammatory studies |
✅ Ion Channels & Neuroimmune Targets
Some research models show ARA-290 interacting with:
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TRPV1 & TRPA1 modulation (nociception studies)
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Macrophage phenotype switching (M1 → M2)
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Microglial signaling alterations
These findings position ARA-290 in models of inflammatory and neuropathic signaling biology.
✅ Why ARA-290 Is Distinct From Erythropoietin
| Property | EPO | ARA-290 |
|---|---|---|
| Binds EPO-R homodimer | ✅ Yes | ❌ No |
| Stimulates erythropoiesis | ✅ Yes | ❌ No |
| Binds EPOR/CD131 IRR | Limited | ✅ Primary target |
| Research focus | Hematopoiesis & EPO biology | Cytoprotective, neuroimmune, anti-inflammatory signaling |
This allows researchers to isolate non-hematopoietic EPO-derived signaling.
Research-Only Classification
ARA-290 is supplied solely for laboratory and in-vitro scientific research.
It is not a drug, supplement, therapeutic agent, or diagnostic material, and is not approved for human or animal use.
