Ara-290, also known by its INN cibinetide and the descriptor pyroglutamate helix B surface peptide (pHBSP), is an 11-amino-acid synthetic peptide derived from the helix B domain of erythropoietin (EPO). It was designed to separate the two receptor systems that full-length EPO engages: the classical EPO receptor homodimer, which drives erythropoiesis, and a heteromeric complex of the EPO receptor with the β-common receptor (CD131), referred to in the literature as the IRR. Ara-290 binds the heteromeric complex without meaningful activation of the homodimer in receptor assays, which makes it a tool compound for studying the two signaling systems separately. This overview covers its chemical identity, receptor pharmacology, published preclinical research context, analytical characterization and laboratory handling.
Sequence: pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser, with pyroglutamate at the N-terminus. The peptide reproduces the solvent-exposed face of EPO helix B, a surface that does not participate in binding the EPOR homodimer.
Length: 11 amino acids. Molecular formula: C51H84N16O21. Molecular weight: approximately 1,257.3 g/mol. Classification: EPO-derived helix B peptide; EPOR/CD131-selective ligand. Originator: Araim Pharmaceuticals (USA).
The N-terminal pyroglutamate forms by cyclization of glutamine. It removes the free N-terminal amine and increases resistance to aminopeptidases.
Full-length EPO signals through two receptor assemblies. The EPOR homodimer activates JAK2 and STAT5 in erythroid progenitors and is responsible for erythropoiesis. The heteromeric EPOR/CD131 complex is expressed at low levels in many non-hematopoietic tissues and is upregulated under cellular stress in experimental systems.
Ara-290 binds the EPOR/CD131 complex and does not meaningfully activate the EPOR homodimer. Published cell-culture and animal studies have examined downstream signaling of this complex, including JAK2, PI3K/Akt and NF-κB pathway components, and NLRP3 inflammasome activity in Schwann-cell models.
Ara-290 has been examined in published in-vitro and animal research on EPOR/CD131 receptor biology, peripheral nerve biology and inflammatory signaling. A 2025 study in the European Journal of Pharmacology examined NLRP3 inflammasome signaling in Schwann cells in a rat sciatic nerve model, comparing Ara-290 with full-length EPO.
Other preclinical work has used Ara-290 alongside full-length EPO and EPO variants to study how receptor composition determines signaling responses in non-hematopoietic cells. Because the peptide lacks erythropoietic activity in these assays, it allows investigators to examine EPOR/CD131 signaling without the hematological changes that full-length EPO produces in animal models.
Ara-290 is studied in: EPO receptor biology, EPOR/CD131 signaling in non-hematopoietic cells, Schwann cell and peripheral nerve biology, inflammatory signaling pathways, and the design of receptor-selective peptides derived from larger cytokines.
Purity is assessed by reverse-phase HPLC and identity by mass spectrometry against the calculated mass of about 1,257 Da. Incomplete pyroglutamate formation yields an N-terminal glutamine variant (+17 Da), which is resolved chromatographically and tracked as a specific impurity.
Ara-290 is assembled by Fmoc solid-phase peptide synthesis. The N-terminal pyroglutamate can be introduced directly as pyroglutamic acid in the final coupling step or formed by controlled cyclization of an N-terminal glutamine. The peptide is then cleaved from the resin, purified by preparative reverse-phase HPLC and lyophilized.
Receptor selectivity is usually demonstrated by comparing signaling in cells that express EPOR alone with cells that co-express EPOR and CD131, with full-length EPO run as a positive control for homodimer activation. Neutralizing antibodies to CD131 or CD131 knockdown help attribute a response to the heteromeric complex, and proliferation of EPO-dependent hematopoietic cell lines provides a counter-screen for homodimer activity.
Ara-290 is not approved by the FDA for human or veterinary use. Material sold as a research chemical is supplied for in-vitro laboratory research and identification purposes only and is not for human consumption.
Form: lyophilized powder. Storage: −20°C, desiccated, protected from light. Avoid repeated freeze–thaw of stock material.
For research use only. Not for human consumption. Not approved by the FDA for human or veterinary use.
EPO is a 165-amino-acid glycoprotein that activates both the EPOR homodimer (erythropoiesis) and the EPOR/CD131 heteromeric complex. Ara-290 is an 11-residue peptide from EPO helix B that binds the heteromeric complex without meaningful activation of the homodimer in receptor assays.
pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser, an 11-residue peptide with an N-terminal pyroglutamate. Molecular formula C51H84N16O21, molecular weight about 1,257.3 g/mol.
CD131 is the shared signaling subunit of the receptors for IL-3, IL-5 and GM-CSF. Together with the EPO receptor it forms the heteromeric complex that Ara-290 binds in receptor studies.
By reverse-phase HPLC for purity and mass spectrometry for identity against the calculated mass of about 1,257 Da, with the N-terminal glutamine variant monitored as a specific impurity.