ARA-290

ARA-290 (cibinetide), also called pyroglutamate helix B surface peptide (pHBSP), is an 11-amino-acid peptide (C51H84N16O21, 1257.3 g/mol) modeled on the three-dimensional structure of erythropoietin (EPO) in the region of helix B. EPO signals through two receptor configurations: an EPOR homodimer that drives maturation of erythroid progenitor cells, and a heteromer of EPOR with the β-common receptor subunit (CD131) found on other cell types, including immune cells. ARA-290 was designed to engage the EPOR/CD131 heteromer selectively, without interacting with the EPOR homodimer.

ARA-290 in the research literature

Research on ARA-290 has centred on EPOR/CD131 heteromer signaling in immune and structural cells. In LPS-activated primary macrophages, the peptide's effects on inflammatory mediator production were reported to depend on CD131 and JAK2 and to involve inhibition of NF-κB p65 activity. In dextran sulphate sodium-exposed mice, it was associated with reduced myeloid-cell infiltration and lower production of cytokines, chemokines and nitric oxide synthase-2.

Other studies have looked beyond the heteromeric receptor. Calcium-imaging and cell-culture experiments reported that ARA-290 specifically inhibited TRPV1 channel activity. In bone biology, the peptide inhibited osteoclastogenesis in vitro and was associated with increased cortical and trabecular bone mineral density in mice, alongside fewer osteoclast progenitors when given with EPO.