ARA 290
Non-erythropoietic peptide derived from erythropoietin (EPO) — activates the innate repair receptor (IRR) for tissue protection and regeneration without stimulating red blood cell production.
🔬 Mechanism of Action
ARA 290 (Cibinetide) is an 11-amino-acid peptide derived from the helix B surface of erythropoietin (EPO). While EPO activates the classical erythropoietin receptor (EPOR homodimer) to stimulate red blood cell production, ARA 290 specifically targets the innate repair receptor (IRR) — a heterodimer of EPOR and βcR (CD131).
The IRR is expressed on neurons, endothelial cells, cardiomyocytes, and immune cells but NOT on erythroid progenitors. This selectivity gives ARA 290 all of EPO's tissue-protective, anti-inflammatory, and anti-apoptotic effects without stimulating erythropoiesis (which causes dangerous polycythemia at therapeutic tissue-protective doses of EPO).
Phase II clinical trials demonstrated efficacy in: sarcoidosis-related small fiber neuropathy (improvement in corneal nerve fiber density and neuropathic pain), diabetic neuropathy (improved nerve function), and chronic heart failure (improved exercise capacity).
Source: PMID: 25074880
📜Background & History
ARA 290 (Cibinetide) was developed by Araim Pharmaceuticals based on research by Anthony Cerami and Michael Brines. The key insight: erythropoietin (EPO) has tissue-protective effects mediated through a different receptor than the one driving erythropoiesis. ARA 290 was designed to specifically target this "innate repair receptor" (EPOR/βcR heterodimer) without stimulating red blood cell production. This allows EPO's neuroprotective, anti-inflammatory, and tissue-regenerative effects at pharmacological doses without the dangerous polycythemia that limits therapeutic EPO use.
🎯 Research Use Cases
- ✓Neuropathy treatment (sarcoidosis, diabetic peripheral)
- ✓Tissue protection and repair after ischemic events
- ✓Anti-inflammatory therapy without immunosuppression
- ✓Neuroprotection in chronic inflammatory conditions
💉 Dosing Protocol
| Typical Dose | 1-4 mg SC |
| Frequency | 1× daily or 3× weekly |
| Half-Life | ~2 minutes |
| Common Vial Sizes | 4 mg, 8 mg |
🧪 Reconstitution Example
⚠️Safety & Considerations
Completed Phase II trials with favorable safety profile. Very short half-life (~2 minutes) — effects are mediated through receptor signaling cascade that outlasts peptide presence. No erythropoietic stimulation — safe for patients where EPO would be contraindicated. Most common side effect: mild injection site reactions.
⚡Interactions & Contraindications
Very short half-life (~2 minutes) — effects mediated through signaling cascades that outlast peptide presence. No erythropoietic stimulation — can be used where EPO is contraindicated. Completed Phase II trials with favorable safety. No significant drug interactions documented.
🔗Synergies & Common Stacks
ARA 290 (systemic tissue protection via innate repair receptor) complements BPC-157 (local tissue repair via growth factor modulation) — multi-pathway tissue regeneration.
Both promote tissue repair through different mechanisms — ARA 290 via innate repair receptor, TB-500 via actin sequestration and cell migration. Complementary wound healing and tissue regeneration.