Adamax

Adamax is a community label for ARA-290 / cibinetide, an 11-amino-acid peptide derived from the helix-B region of erythropoietin (EPO). Unlike full-length EPO, ARA-290 has no effect on red-blood-cell production but retains the tissue-protective and anti-inflammatory activity of EPO via the innate-repair receptor (IRR, a heterodimer of EPOR and CD131).

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / Adamax](https://peppudex.com/peptides/adamax).

Overview

ARA-290 was developed by Araim Pharmaceuticals (now Pharnext) as a small-peptide analog of EPO that decouples hematopoiesis from tissue-protection. The sequence corresponds to amino acids 58-82 of human EPO (the helix-B surface peptide region). The compound is sometimes referred to in research circles as cibinetide.

Mechanism

The proposed mechanism is signaling through the innate-repair receptor, a heterodimer of the EPO receptor and the common beta-chain (CD131). This receptor is upregulated in injured tissue, drives anti-inflammatory and pro-survival gene expression via STAT3, and does not promote erythropoiesis. ARA-290 selectively activates this receptor without binding the homodimeric EPOR2 that drives RBC production.

See: Angiogenesis, Nitric_oxide_signaling.

Evidence

Clinical evidence is concentrated in two areas:

• Sarcoidosis small-fiber neuropathy · Phase 2 trials (Heij et al., 2012; Dahan et al., 2013) showed improvement in pain scores and quality-of-life measures in patients with sarcoidosis-associated small-fiber neuropathy.
• Diabetic macular edema · Phase 2 trial in patients with diabetic macular edema reported visual-acuity improvement (Dahan et al., 2017).

Animal-model evidence covers ischemia-reperfusion (kidney, heart), neuropathic pain, and bone healing.

Dosing literature

Clinical trials have used subcutaneous 4 mg/day in adults with sarcoidosis-related neuropathy. The wiki does not recommend any human dose; ARA-290 is investigational and not FDA-approved.

Pharmacokinetics

ARA-290 has a plasma half-life of approximately 2 minutes after subcutaneous injection due to rapid renal clearance and proteolytic cleavage. Despite the short half-life, downstream cellular effects on the innate-repair receptor persist much longer, similar to the way short-half-life cytokines produce sustained transcriptional effects. Daily subcutaneous dosing is the standard published protocol.

Storage

Lyophilized ARA-290 is stable at –20 °C for at least 24 months. After reconstitution with bacteriostatic water, store at 2-8 °C and use within 28 days.

Regulatory status

• United States. Investigational. Not FDA-approved. Orphan-drug designation granted for sarcoidosis-related small-fiber neuropathy.
• WADA. EPO and EPO-derivatives are prohibited under S2 (peptide hormones, growth factors) on the WADA Prohibited List. ARA-290's hematologically inactive profile has not exempted it from class-wide treatment.

Side effects (per published Phase 2)

Heij 2012 and Dahan 2013 Phase 2 trials reported a benign safety profile. No significant adverse-event signals beyond mild injection-site reactions. As an EPO-family compound, theoretical concerns about hematologic effects exist, but the published data show no significant change in hemoglobin or hematocrit at clinical doses · consistent with the molecule's selective innate-repair-receptor activation and absence of EPOR2 homodimer binding.

See also

• Nitric_oxide_signaling · downstream of innate-repair receptor activation
• Reconstitution · vial-prep math
• [Peppudex card · Adamax](https://peppudex.com/peptides/adamax) · mechanism, evidence grades A-F, FAQs, peer-reviewed sources

References

• Brines M, Cerami A. "Discovering erythropoietin's extra-hematopoietic functions: biology and clinical promise." Kidney Int. 2006;70(2):246-50. PMID 16738535.
• Heij L, et al. "Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study." Mol Med. 2012;18:1430-6. PMID 23168581.
• Dahan A, et al. "Identification of cibinetide as a potent treatment for type-2 diabetes-associated subclinical neuropathy." Front Pharmacol. 2017;8:855. PMID 29225582.