ARA-290 (Cibinetide)
Non-hematopoietic erythropoietin analog researched for neuropathic pain and tissue protection
Half-life
~2 min (but long biological effect)
Typical Dose
4-16 mg daily
Format
Injectable
Purity
≥98%
Overview
ARA-290 (Cibinetide) is an 11-amino-acid peptide derived from the helix B domain of erythropoietin (EPO). Unlike EPO itself, it does not bind the classical erythropoietin receptor homodimer and therefore does not stimulate red blood cell production — but it retains the tissue-protective and anti-inflammatory effects of EPO by activating the innate repair receptor. It has been studied in clinical trials for diabetic neuropathic pain and sarcoidosis-associated small fiber neuropathy.
Mechanism
ARA-290 binds the innate repair receptor (IRR), a heterodimer composed of the EpoR and CD131 (common beta receptor) subunits. This receptor is distinct from the EpoR homodimer that mediates red blood cell production, which is why ARA-290 does not raise hematocrit. IRR activation triggers anti-apoptotic, anti-inflammatory, and tissue repair signaling — the tissue-protective arm of EPO biology without the hematopoietic effects.
Researched benefits
- Neuropathic pain research
- Diabetic peripheral neuropathy studies
- Sarcoidosis-associated small fiber neuropathy
- Tissue protection and repair
- Anti-inflammatory without hematopoietic effects
- No hematocrit elevation (unlike EPO)
Frequently asked
Why doesn't ARA-290 raise red blood cell count like EPO?
EPO's erythropoietic effect requires binding the EpoR homodimer on red blood cell precursors. ARA-290 was engineered to retain affinity only for the innate repair receptor — a heterodimer of EpoR and CD131 found on tissues involved in repair and inflammation. Because it doesn't engage the EpoR homodimer, it does not drive erythropoiesis.
How can a 2-minute half-life produce sustained effects?
Similar to DSIP, ARA-290 acts as a trigger — once it activates the innate repair receptor, downstream signaling cascades (STAT3, Akt) persist long after the peptide is cleared. Clinical trials used daily subcutaneous dosing and reported sustained effects on pain and small fiber density over weeks.
What conditions has ARA-290 been studied for in humans?
Published clinical trials have investigated ARA-290 for sarcoidosis-associated small fiber neuropathy and diabetic peripheral neuropathy, with reports of improvements in neuropathic pain, small fiber nerve density, and quality-of-life metrics. It has also been studied in more exploratory contexts for tissue protection.
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