ARA-290 (also known as Cibinetide) is a synthetic, non-hematopoietic peptide analog of erythropoietin (EPO). It’s an 11-amino-acid sequence derived from the EPO receptor’s binding domain, specifically designed to activate the innate repair receptor (IRR), a heteromer of the EPO receptor and β-common receptor. Unlike full EPO, it doesn’t stimulate red blood cell production, avoiding risks like thrombosis.

Key Facts:

• Molecular Formula: C118H211N37O40S2 (approximate for the active sequence).
• Molecular Weight: ~2,500 Da.
• CAS Number: 1055250-52-2.
• Half-Life: ~20-30 minutes in plasma, but effects can last days due to tissue repair mechanisms.

Mechanism of Action

ARA-290 selectively binds to IRR on tissue macrophages and neurons, promoting:

• Anti-inflammatory effects by reducing pro-inflammatory cytokines (e.g., TNF-α, IL-6).
• Neuroprotection and tissue repair via activation of anti-apoptotic pathways (e.g., PI3K/Akt, MAPK/ERK).
• Improved nerve conduction and pain modulation through normalization of sodium channels (e.g., Nav1.7, Nav1.8).

Evidence:

• Preclinical studies (e.g., rat models of diabetic neuropathy) show it restores epidermal nerve fiber density and improves sensory function (Brines et al., PNAS 2014).
• IRR activation is tissue-protective without hematopoietic effects, confirmed in knockout mouse models (Mol Med 2015).

Potential Uses and Research

ARA-290 is investigational and not FDA-approved for any indication. It’s primarily studied for:

Clinical Trial Summary (from ClinicalTrials.gov):

• ~10 trials, mostly Phase I/II by Araim Pharmaceuticals.
• Doses: 2-4 mg/day subcutaneous for 4-28 weeks.
• Safety: Well-tolerated; mild injection-site reactions common, no serious adverse events in trials.

Availability and Legality

• Not approved by FDA, EMA, or equivalents for human use.
• Sold as research chemical by peptide suppliers (e.g., 2-10 mg vials, ~$50-200).
• Legal Status: Unscheduled in most countries, but human consumption is unregulated and risky. Banned by WADA for athletes.
• Often reconstituted with bacteriostatic water for research (e.g., 2 mg vial in 2 mL = 1 mg/mL).

Risks and Side Effects:

• Limited human data; potential for immunogenicity or off-target effects.
• Theoretical risks: Allergic reactions, unknown long-term effects.
• Not for self-administration—consult a physician. Purity varies in research-grade products (third-party testing recommended).

Recent Developments

• Araim Pharmaceuticals (developer) shifted focus post-2020; no active recruitment.
• Ongoing interest in neuropathic pain; 2023 preclinical data on post-COVID neuropathy (bioRxiv preprint).

For sourcing or protocols, refer to primary literature (PubMed: “ARA-290” yields ~50 papers). Always prioritize evidence-based medicine—it’s experimental, not a miracle cure. If you’re researching for a specific condition, share more details for tailored refs.