Ara-290 (Cibinetide)

Product Overview

ARA-290 was developed from a deep understanding of cellular stress signaling and innate repair mechanisms. Unlike full-length erythropoietin, ARA-290 does not bind the classical erythropoietin receptor, does not increase hematocrit, and does not stimulate bone marrow erythropoiesis. Instead, it selectively activates anti-inflammatory and cytoprotective pathways via the β-common receptor, which becomes up-regulated following tissue injury or inflammation.

Mechanism of Action

ARA-290 activates the β-common receptor/EPO receptor heterocomplex, which is locally up-regulated at sites of tissue injury. It works on the central nervous system to support nerve regeneration, inhibits the NLRP3 inflammasome by suppressing NF-κB phosphorylation, and reduces reactive oxygen species production. Its action is immunomodulatory rather than immunosuppressive, calming excessive inflammation while preserving natural immune defenses.

Key Benefits

Nerve Repair & Pain Relief — Clinical studies show ARA-290 improves neuropathic symptoms in diabetic neuropathy patients. Objective evidence demonstrates increased corneal nerve fiber density, indicating structural nerve regeneration rather than just symptom masking.

Ischemic Injury Protection — ARA-290 protects tissues from hypoxia, ischemia-reperfusion injury, and oxidative stress. It reduces caspase-3 expression (a key apoptosis marker) through the PI3K/Akt signaling pathway and enhances endothelial colony-forming cell function for vascular repair.

Anti-Inflammatory Signaling — Reduces pro-inflammatory cytokines (IL-1β, IL-17, TNF-α, IFN-γ) by inhibiting the NLRP3 inflammasome and NF-κB pathway. Importantly, this is immunomodulatory, not immunosuppressive.

Autoimmune & Neuropathy Support — In experimental models, ARA-290 reduces autoimmune severity, promotes nerve regeneration and remyelination, and favors anti-inflammatory Th2 and regulatory T cell polarization.

References

1. Al-Onaizi MA, et al. Early monocyte modulation by the non-erythropoietic peptide ARA 290 decelerates AD-like pathology progression. *Brain Behav Immun.* 2022;99:363–382.
2. Bohr S, et al. Alternative erythropoietin-mediated signaling prevents secondary microvascular thrombosis within cutaneous burns. *PNAS.* 2013;110(9):3513–3518.
3. Brines M, Cerami A. Erythropoietin-mediated tissue protection. *J Intern Med.* 2008;264:405–432.