Ara-290 (Cibinetide) is an 11-amino acid EPO-derived peptide that selectively activates the innate repair receptor (IRR) for tissue-protective signaling research without erythropoietic effects.
Ara-290, also known by its development name Cibinetide, is a rationally designed 11-amino acid synthetic peptide with the sequence Gln-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (QEQLERALNSS). The peptide was engineered by Araim Pharmaceuticals based on the three-dimensional spatial relationship of amino acid residues on the B-helix surface of erythropoietin (EPO) that mediate tissue-protective — rather than erythropoietic — signaling. This structure-guided approach produced a peptide that replicates the cytoprotective geometry of EPO while completely lacking the ability to stimulate red blood cell production.
Ara-290 selectively engages the innate repair receptor (IRR), a heterodimeric complex consisting of the erythropoietin receptor (EPOR) and the beta common receptor (βcR, also known as CD131). This receptor is distinct from the classical homodimeric EPOR that drives erythropoiesis, and its activation triggers anti-apoptotic and anti-inflammatory signaling cascades including JAK2/STAT5, PI3K/Akt, and NF-κB modulation. The IRR is expressed on neurons, Schwann cells, endothelial cells, monocytes, and other tissue-resident cells involved in damage response, making it a broad tissue-protective signaling node.
In published research, Ara-290 has been studied in models of neuropathic signaling, diabetic neuropathy, cardiac ischemia-reperfusion injury, chronic inflammatory conditions, and metabolic stress. Notably, its non-erythropoietic profile eliminates concerns about hematocrit elevation and thrombotic risk that complicate the use of EPO itself in tissue-protection research. This selectivity makes Ara-290 a uniquely valuable tool for isolating tissue-protective EPO signaling from classical erythropoietic pathways. Research has also explored its effects on corneal nerve regeneration, sarcoidosis-related small fiber neuropathy models, and Type 2 diabetes-associated nerve damage paradigms.
Published preclinical and translational data include studies demonstrating IRR-dependent neuroprotection in sensory neuron models, reduced inflammatory cytokine production in macrophage cultures, and improved nerve fiber density in corneal confocal microscopy assessments. These findings span multiple independent research groups and peer-reviewed journals, establishing Ara-290 as a well-documented tool for IRR pathway investigation.
Supplied as a lyophilized powder with ≥99% purity confirmed by RP-HPLC and ESI-MS. Certificate of Analysis provided with each lot. Store at -20°C desiccated and protect from light, as the peptide contains light-sensitive residues. Reconstitute with sterile water prior to experimental use. For in vitro and laboratory research applications only.
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