ARA-290 (INN/USAN: cibinetide; INN number 10264; also called PHBSP / pHBSP / pyroglutamate helix B surface peptide) is an investigational 11-residue synthetic peptide modeled on the aqueous face of helix B of erythropoietin. It is not erythropoietin, not an ESA (erythropoiesis-stimulating agent), and not FDA-approved. Identity below is taken from pages that were opened: NCATS Inxight Drugs (UNII 9W5677JKDA), PubChem CID 91810664 (PUG REST properties and synonyms), and IUPHAR/BPS Guide to Pharmacology ligand 9677.

Registered cibinetide is the pyroglutamate form. Three-letter sequence from NCATS systematic names and PubChem synonyms: Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser-OH (N-terminus is pyroglutamate / 5-oxo-L-proline). One-letter forms used on opened registry pages: XEQLERALNSS / UEQLERALNSS, with X = pyroglutamate. PubChem synonyms list UEQLERALNSS; the IUPHAR structure tab listed XEQLERALNSS.

The 2008 design paper described an 11-mer helix B surface peptide (HBSP) as QEQLERALNSS (N-terminal glutamine), assembled from aqueous-face residues of EPO helix B plus three proximal BC-loop residues (PMID 18676614). Literature and vendor pages sometimes use HBSP, pHBSP, PHBSP, and ARA-290 interchangeably. The research peptide on a vendor vial is not independently confirmed here to match the registered cibinetide salt/form or the clinical-trial material (Bachem-manufactured peptide was used in the opened type 2 diabetes trial).

No UniProt accession applies. This is a synthetic peptide, not a natural gene product. The FDA GSRS HTML page for UNII 9W5677JKDA was requested but returned no usable body text; UNII and CAS were taken from the opened NCATS Inxight record and PubChem synonyms. DrugBank DB13006 was requested; the page was blocked by Cloudflare and was not used as a source of facts.

Erythropoietin (EPO) is a type 1 cytokine best known as the hormonal regulator of red-cell production. That hematopoietic activity is mediated by the classical EPOR homodimer (Brines et al., 2004, PMID 15456912; Brines et al., 2008, PMID 18676614).

Separately, EPO and some EPO derivatives have been studied for tissue-protective, anti-inflammatory, and anti-apoptotic effects in injured or metabolically stressed tissues. Leist et al. (2004, PMID 15247477) reported that carbamylated EPO (CEPO) and certain EPO mutants did not bind classical EPOR, did not stimulate hematopoiesis, and were still cytoprotective in animal models of stroke, spinal-cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis. CEPO is a chemically modified full-length EPO protein. It is related in concept (non-hematopoietic tissue protection) but chemically distinct from ARA-290.

Brines et al. (2008, PMID 18676614) then delimited tissue-protective activity to short peptides from EPO helix B (residues 58–82), which faces solvent when EPO is bound to the EPOR homodimer. An 11-aa peptide simulating that aqueous face (HBSP: QEQLERALNSS) was tissue-protective in rodent models of ischemic stroke and renal ischemia–reperfusion, accelerated wound healing, and augmented cognitive function in rodents, and was not erythropoietic in vitro or in vivo. ARA-290 / cibinetide is the later pyroglutamate-stabilized clinical-development peptide built on that helix-B-surface idea (Brines et al., 2015, PMID 25387363, describe ARA 290 as “an 11-amino acid peptide modeled from the three dimensional structure of helix B of the EPO molecule,” MW 1257 Da).

The mechanism literature is a working hypothesis with conflicting biochemistry. Hypothesis means the innate repair receptor (IRR) / tissue-protective receptor as proposed in opened papers. Observed means a functional result in an opened model. Contrary means opened biophysics that did not detect the proposed extracellular complex. There is no invented receptor diagram on this page.

The hypothesis (opened primary papers and reviews). Brines et al. (2004, PMID 15456912) proposed that EPO’s tissue-protective actions use a heteroreceptor of EPOR plus the common β subunit (βc / CD131; shared by GM-CSF, IL-3, and IL-5 receptors), because: (i) CEPO was tissue-protective without binding classical EPOR; (ii) EPOR and βc co-purified / co-immunoprecipitated from rat organ membranes and P19 cells; (iii) the two subunits colocalized on protected neurons and cardiomyocytes; and (iv) neither EPO nor CEPO was active in cardiomyocyte or spinal-cord injury models in βc knockout mice. βc is not required for erythropoiesis (βc knockout mice have normal erythrocyte maturation).

Brines and Cerami (2012, PMID 22183892) later called this the tissue-protective receptor / innate repair receptor (IRR): generally not expressed on normal tissue, upregulated after injury, hypoxia, or metabolic stress, and composed of CD131 plus the same EPOR subunit used in erythropoiesis (with VEGF receptor also discussed as a possible component in endothelium). They argued that locally produced EPO is delayed and weak relative to the injury response, creating a window for exogenous ligands that prefer the tissue-protective receptor over the hematopoietic homodimer.

ARA-290 is described in later opened papers as a selective IRR / EPOR–CD131 agonist that does not stimulate the hematopoietic EPOR homodimer (Heij 2012; Dahan 2013; Brines 2015; Nairz 2017; Bitto 2017). Swartjes et al. (2011, PMID 21873879) reported that ARA290 relieved tactile and cold allodynia after spared-nerve injury in rats and in wild-type mice, but not in β-common-receptor knockout mice — a functional genetic argument that βc is required for that preclinical analgesia signal.

Nairz et al. (2017, PMID 29026145) reported that cibinetide’s anti-inflammatory effects on LPS-activated primary macrophages were dependent on CD131 and JAK2 and involved inhibition of NF-κB p65, in a mouse DSS-colitis model.

Opened work falls into three layers. None of it is a substitute for controlled laboratory characterization of a specific vial. Opened human research is Phase 1–2 only, mostly small, often single-center, often with Araim employees as authors, and without an opened Phase 3 program. Several symptom scales moved in placebo arms. That is the evidence map, not a proof of clinical effectiveness.

Read the “what was actually studied” column first. Published study designs are historical facts from those papers. They are not a protocol. Clinical-trial doses appear only as historical study conditions. They are not use instructions for a research peptide and are not a recommended human dose.

Clinical-trial doses appear below only as historical study conditions. They are not use instructions for a research peptide and are not a recommended human dose. Seven human-study records were opened: four published interventional papers with full or abstract text (Heij 2012; Dahan 2013; Brines 2015; Culver 2017), one published DME pilot (Lois 2020), one published healthy-volunteer cognition paper (Cerit 2015), plus the Karolinska registry record without results (NCT01933529). That is six published human studies and one result-less registry trial. No Phase 3 record was present in the opened ClinicalTrials.gov API result set.

ARA-290 sold as a research peptide is a laboratory reagent. It is not erythropoietin, not an ESA, and not FDA-approved. It is not a dietary supplement, and is not for human or veterinary use, consumption, administration, diagnosis, or treatment. This page is educational. It does not provide dosing, reconstitution, administration, or any human-use instructions. No human dosing protocol appears here.

SRP material is for laboratory research only. Research use only.

Laboratory identity is the first practical issue. Confirm sequence (including N-terminal pyroglutamate vs free Gln), mass (~1257.3 Da for the free peptide), and purity by orthogonal methods. Registered cibinetide is XEQLERALNSS (Pyr-EQLERALNSS; CAS 1208243-50-8). The 2008 HBSP design sequence is QEQLERALNSS. Do not assume a lyophilized “ARA-290 10 mg” vial matches Bachem clinical-trial cibinetide. The opened SRP page listed no sequence, CAS, COA, or manufacturer.

Biological inference has the same problem. A 28-day corneal-nerve-area signal at 4 mg/day in sarcoidosis SFN, mixed symptom scales that also moved on placebo, a DME pilot that missed its primary vision endpoint, and a cognition study that did not support an antidepressant-like profile are not interchangeable with marketplace claims about nerve regeneration, recovery, or mood. IRR is a hypothesis; Cheung Tung Shing 2018 found no extracellular EPOR–βc association.

Pharmacokinetics quoted from the opened diabetes paper (peak ~3 ng/mL, t½ ~20 min after 4 mg SC) describe clinical-trial product in volunteers, not a reconstituted research vial, and are not a dosing guide.

Full citations for the verified set. Each line is a paper or registry record actually opened for this draft. Do not add PMIDs that are not on the allowed list. Cheung Tung Shing 2018 is DOI-only; no PMID was taken from the opened page.

Allowed PMID list used on this page: 15456912, 15247477, 18676614, 21873879, 22183892, 23168581, 24136731, 24555851, 25387363, 26431906, 28475703, 29026145, 29223734, 30876881, 32674280. DOI-only: 10.1038/s41598-018-29865-x. No other PMIDs were added.

Product links are research materials, not treatment recommendations.