ARA-290 Research Standard
ARA-290 (CAS 1208243-50-8), also indexed as cibinetide and as pyroglutamate helix B surface peptide (pHBSP), is an 11-amino-acid peptide modelled on the three-dimensional structure of erythropoietin in the region of helix B. Supplied as a 10 mg lyophilized powder in a 3 mL vial, it exists to separate two effects of EPO that turn out to run through different receptors.[1]
Mechanism of Action & Research Context
Two receptors, one hormone. Erythropoiesis is driven by EPO binding an EPOR homodimer. Tissue protection and repair is driven by a distinct heterodimeric complex of EPOR and the β common receptor subunit, termed the innate repair receptor (IRR). ARA-290 was engineered to activate the IRR selectively, without interacting with the EPOR homodimer.[1]
Why the separation matters. Recombinant EPO’s tissue-protective use is limited by what the erythropoietic arm does alongside it — rising haematocrit, platelet activation and selectin expression, carrying thrombosis risk. A ligand that engages only the repair arm removes that confound.[1]
The IRR is injury-inducible, not constitutive. It is typically not expressed by normal tissue, but is rapidly induced by injury or inflammation. So the target only appears where the tissue is already stressed — which means an unperturbed control preparation may have nothing for the ligand to bind.[1]
A two-minute half-life with lasting effects. Plasma half-life is roughly 2 minutes, yet the peptide triggers sustained biological effects across multiple experimental models. The framing in the literature is a molecular switch rather than sustained occupancy — and it is a warning against inferring duration of effect from pharmacokinetics.[1]
It is not simply an EPO substitute. In a murine model, pHBSP attenuated renal oxidative and nitrosative stress and reduced tubular dedifferentiation, while EPO did not attenuate nitrosative stress. The two ligands give measurably different profiles.[2]
Handling
Soluble in phosphate buffered saline near pH 7.4. Poorly soluble in the standard research diluent, which sits closer to neutral. Kimera Chems does not stock PBS.
Research Applications
Primary fields of in vitro and preclinical laboratory investigation include:
Receptor-selectivity studies separating IRR from EPOR homodimer engagement.[1]
Injury-induced receptor expression assays, since the IRR appears only on stressed tissue.[1]
Oxidative and nitrosative stress readouts, run in parallel because the two dissociate.[2]
Pharmacokinetic/pharmacodynamic dissociation studies, where effect outlasts exposure by orders of magnitude.[1]
Comparative work against recombinant EPO.[2]
Analytical Documentation
Purity and identity vary by manufacturing lot. Kimera Chems does not publish a single fixed purity figure for this item; refer to the batch-specific Certificate of Analysis (COA) issued for the lot received, which reflects third-party analytical testing for that lot.
References
- Collino M, Thiemermann C, Cerami A, Brines M. Flipping the molecular switch for innate protection and repair of tissues: long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin. Pharmacol Ther. 2015;151:32–40. doi:10.1016/j.pharmthera.2015.02.005
- Dennhardt S, Pirschel W, Wissuwa B, et al. Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice. Front Immunol. 2022;13:1010882. doi:10.3389/fimmu.2022.1010882
Storage & Handling
Store at controlled room temperature, sealed and protected from light.
Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.
