Key findings
- The design work separates two receptors: hematopoiesis through the erythropoietin receptor homodimer and tissue protection through a heterocomplex of that receptor with CD131, and it reports that neither helix B nor the eleven-residue peptide was erythropoietic in vitro or in vivo. [1]
- A bone study used the peptide specifically because it binds the heteromeric receptor exclusively, and found that it inhibited osteoclastogenesis in culture. [2]
- Isolated human islets held in a pro-inflammatory cytokine environment retained ATP content, showed reduced caspase 3 and 7 activity and improved insulin secreting capacity in the presence of the peptide, and platelet consumption fell in a blood loop model. [3]
- In three cultured cell types the peptide reduced DNA damage measured by comet assay and micronucleus frequency after a doxorubicin challenge, and in endothelial colony forming cells it activated pro-survival signalling and raised viability under hydrogen peroxide stress. [4][5]
Identity and structure
- Length and origin
- Eleven amino acid residues composed of adjacent residues that form the aqueous face of helix B of erythropoietin [1]
- Parent region
- Helix B spans residues 58 to 82 of erythropoietin and faces the aqueous medium when the protein is bound to the receptor homodimer [1]
- Receptor engaged in cited work
- The heterocomplex of the erythropoietin receptor with CD131, the beta common receptor, rather than the erythropoietin receptor homodimer [1][2]
- Not the parent protein
- A short structural mimic of one face of one helix is not erythropoietin; the cited work reports the peptide as non-erythropoietic in vitro and in vivo while the parent protein is not [1]
- Modified constructs in the literature
- One cited paper used a chelated, radiolabelled construct with Arg6 and Ala7 replaced by a dabcyl-lysine and a phenylalanine, which is a different material from the unmodified peptide [6]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The founding argument is structural. Erythropoietin carries two separable functions through two receptors, and the tissue-protective one was narrowed to short sequences within helix B. Because the aqueous face of that helix is exposed when the protein sits on the receptor homodimer, a peptide reproducing only that face engages the heterocomplex while leaving the erythropoietic receptor untouched, which the authors confirmed by finding no erythropoietic activity in vitro or in vivo. [1]
Subsequent work uses that receptor selectivity as a tool. The bone study chose the peptide precisely because it binds the heteromeric receptor exclusively and compared it against erythropoietin, which acts at both, to separate the two receptors' contributions to osteoclast progenitor numbers and osteoclastogenesis. [2]
Downstream readouts across the cited cell work are consistently stress related rather than proliferative: pro-survival signalling and viability under hydrogen peroxide in endothelial colony forming cells, reduced reactive oxygen species and NF-kappaB phosphorylation with suppressed NLRP3 inflammasome activation in Schwann cells, and attenuated oxidative and genotoxic damage in three cultured cell types. [5][7][4]
Research findings
In vitro
- System
- Neuroprotection assays in culture plus rodent models of ischemic stroke, diabetes induced retinal edema, peripheral nerve trauma and renal ischemia-reperfusion, comparing full erythropoietin, helix B and the eleven-residue peptide
- Measured
- Delimitation of tissue-protective domains within erythropoietin to short peptide sequences, neuroprotection in vitro, tissue protection across the animal models, wound healing and cognitive readouts in rodents, and erythropoietic activity in vitro and in vivo
- Reported
- Helix B was neuroprotective in vitro and tissue protective across the animal models, and the eleven-residue peptide formed from its aqueous face reproduced that activity in ischemic stroke and renal ischemia-reperfusion models as well as the wound healing and cognitive readouts. Neither helix B nor the eleven-residue peptide was erythropoietic in vitro or in vivo. [1]
In vitro
- System
- Osteoclastogenesis cultures, with C57BL/6J mice reported alongside, comparing the peptide alone against erythropoietin and against the two combined
- Measured
- Osteoclastogenesis in culture, the number of osteoclast progenitors defined by flow cytometry, and cortical and trabecular bone mineral density in the animal arm
- Reported
- The peptide, alone or combined with erythropoietin, inhibited osteoclastogenesis in vitro. In the animal arm it raised cortical bone mineral density by about 5.8 percent and trabecular by about 5.2 percent, and reduced the number of osteoclast progenitors by 42.8 percent against erythropoietin alone. [2]
Ex vivo
- System
- Isolated human islets cultured with pro-inflammatory cytokines for 18 hours, and islets rotated with ABO compatible blood in a heparinised polyvinyl chloride tubing loop, with an athymic mouse arm reported alongside
- Measured
- Islet ATP content, caspase 3 and 7 activity, insulin secreting capacity by dynamic glucose perfusion, and platelet consumption in the blood loop
- Reported
- The peptide maintained islet ATP content and reduced caspase 3 and 7 activity during culture with pro-inflammatory cytokines, and improved the insulin secreting capacity of the islets. In the blood loop it reduced the platelet consumption driven by the instant blood mediated inflammatory reaction. [3]
In vitro
- System
- HepG2 cells, human gingival fibroblasts and stem cells, pretreated with the peptide before a doxorubicin challenge
- Measured
- Cytotoxicity by MTT assay, DNA damage by micronucleus test and comet assay, antioxidant defence enzyme activities, and markers of inflammation and apoptotic cell death
- Reported
- The peptide significantly reduced the percentage of DNA in the comet tail and the frequency of micronuclei induced by doxorubicin, and attenuated the doxorubicin driven oxidative stress, inflammation and apoptotic cell death in the three cell types. [4]
Analytical
- System
- A chelated, technetium-99m labelled construct with Arg6 and Ala7 substituted by a dabcyl-lysine and a phenylalanine, rather than the unmodified peptide, tested against hypoxic and normoxic H9c2 cells and in a rat cardiac ischemia model
- Measured
- Radiochemical purity by thin layer chromatography, stability of the radiopeptide in the presence of human serum, binding to hypoxic against normoxic cells, and biodistribution with SPECT imaging
- Reported
- Radiolabelling purity exceeded 96 percent and in vitro stability of the radiopeptide reached 85 percent at six hours. Binding to hypoxic cells was about three times that to normoxic cells at one hour, and the radiopeptide accumulated in the ischemic region in the animal arm. [6]
Preclinical in vivo
- System
- Rat sciatic nerve crush injury with Schwann cells examined after injury, comparing the peptide against erythropoietin
- Measured
- Early inflammatory response and functional recovery after crush injury, NLRP3 inflammasome activation in Schwann cells, NF-kappaB phosphorylation and reactive oxygen species production
- Reported
- Both erythropoietin and the peptide inhibited the early inflammatory response and were followed by functional recovery. NLRP3 inflammasome activation in Schwann cells was inhibited, and the authors attribute that to reduced NF-kappaB phosphorylation and lower reactive oxygen species production. [7]
In vitro
- System
- Endothelial colony forming cell cultures under hydrogen peroxide stress, with an oxygen induced retinopathy mouse model reported alongside and erythropoietin tested in parallel
- Measured
- Pro-survival signalling and cell viability in culture, effects of preconditioning the cells before transfer, and inflammatory cytokine expression and microglial activation in the animal arm
- Reported
- The peptide activated pro-survival signalling and raised viability of the cultured cells under hydrogen peroxide stress. Preconditioning the cells with either the peptide or erythropoietin before transfer did not enhance their vascular repair function, while the peptide present in the animal arm did enhance it and erythropoietin did not. [5]
Handling for in-vitro work
- Assay medium in cited work
- Added to islet culture medium alongside pro-inflammatory cytokines for an 18 hour incubation in the cited ex-vivo work [3]
- Serum stability of a modified construct
- The chelated radiolabelled construct retained 85 percent stability in the presence of human serum over six hours; this figure belongs to that construct and not to the unmodified peptide [6]
- Storage
- Lyophilized at -20 °C, dark and dry; reconstituted aliquots kept cold and used promptly
Open questions
- The cited work does not state the amino acid sequence of the eleven-residue peptide, so a supplied lot needs its own sequence confirmation rather than a match by name.
- Results for erythropoietin itself belong to a receptor pair the peptide does not fully share, and the cited work keeps the two apart as distinct materials.
- One cited imaging paper used a doubly substituted, chelated and radiolabelled construct, so its binding and stability numbers do not transfer to the unmodified peptide.
- The cited studies span islets, bone, nerve, retina and three cultured cell lines with different readouts, and none of them establishes a common downstream measurement that would let the results be compared.
A clinical literature on this peptide exists and concerns finished formulations; it is out of scope for a research material profile.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
No published lot is available for this exact compound name.
Read a certificate of analysis ↗References
- Brines M, Patel NS, Villa P, et al. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proceedings of the National Academy of Sciences of the United States of America. 2008.
- Awida Z, Bachar A, Saed H, et al. The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice. International journal of molecular sciences. 2021.
- Yao M, Domogatskaya A, Ågren N, et al. Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation. Cell transplantation. 2021.
- Shokrzadeh M, Etebari M, Ghassemi-Barghi N An engineered non-erythropoietic erythropoietin-derived peptide, ARA290, attenuates doxorubicin induced genotoxicity and oxidative stress. Toxicology in vitro : an international journal published in association with BIBRA. 2020.
- O'Leary OE, Canning P, Reid E, et al. The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic. Experimental eye research. 2019.
- Mohtavinejad N, Hajiramezanali M, Akhlaghi M, et al. Synthesis and evaluation of 99mTc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region. Iranian journal of basic medical sciences. 2021.
- Liu G, Li W, Jiang S, et al. ARA290, an alternative of erythropoietin, inhibits activation of NLRP3 inflammasome in schwann cells after sciatic nerve injury. European journal of pharmacology. 2025.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.