ARA-290 16mg

▎ARA-290 Structure

▎ARA-290 Research

Molecular Background

ARA290 (also known as Cibinetide) is a synthetic 11-amino-acid peptide designed from the helix B surface region of erythropoietin. PubChem records the sequence as pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (XEQLERALNSS), with the molecular formula C51H84N16O21 and a molecular weight of 1257.3 g/mol.[1,9]

Research Progress
Nolan M. Winicki and colleagues conducted a 15-month animal study combining longitudinal (n = 48) and cross-sectional (n = 144) cohorts of Fischer 344 × Brown Norway rats. Echocardiography, tail-artery blood-pressure measurements, body weight, frailty scoring, tissue inflammatory markers, left-ventricular remodeling, isolated cardiomyocyte measurements, and survival analyses were included in the study design. The authors reported group differences over time in cardiac inflammatory markers, cardiomyocyte autophagy and lipofuscin accumulation, mitochondrial permeability-transition responses, blood pressure, left-ventricular ejection fraction, body weight, and frailty measures under the conditions of the aging model.[2]

Fig1. Echocardiographic measurements reported in the longitudinal ARA290 aging study, including left-ventricular volume, ejection fraction, posterior-wall thickening, and interventricular-septum thickening.[2]

Loess smooth curves (Red = Saline, Blue = ARA290) with 95% confidence intervals (gray) depict age-associated changes in left ventricular volume (A), ejection fraction (B), posterior wall thickening percentage (C), and interventricular septum thickening percentage (D). Statistically significant group-by-time interactions reported by the authors are shown (*P < 0.05).[2]

Guixian Liu and colleagues established a rat sciatic nerve crush injury model using 86 experimental rats and compared normal, injury, EPO, and ARA290 study groups. Nerve tissue and Schwann-cell experiments were used to examine inflammatory-cell infiltration, NLRP3 inflammasome activation, NF-kB phosphorylation, and reactive oxygen species. The authors reported reduced NLRP3 inflammasome activation in Schwann cells in the EPO and ARA290 groups and associated these observations with lower NF-kB phosphorylation and reactive oxygen species under the experimental conditions described.[3]

Fig2. EPOR expression and localization evaluated in Schwann cells and rat sciatic nerve in the study by Liu et al.[3]

(A) The rat sciatic nerves of the control group were exposed for only 1 min, and the sciatic nerves of injury group were pinched by right-angle forceps for 1 min. (B) Comparison of left and right paw of rat sciatic nerve in injured group and control group. (C) HE staining of normal and injured nerves. Scale bar: 100 μm. (D) Immunofluorescence staining results show the infiltration of Macrophages and Schwann cells after nerve injury. (E) EPOR was present in RSC96 cells, and EPOR expression levels increased after stimulation with LPS (1 μg/mL for 24 h) and ATP (5 nM for 30 min). (F) The results of Western blot experiment showed that EPOR existed in rat Schwann cell, and EPOR expression was up-regulated 24 h after nerve injury. (G) The results of immunofluorescence staining showed that EPOR was localized in Schwann cells of rat sciatic nerve. Scale bar: 50 μm. Data are expressed as the mean ± SD of three independent experiments. (n = 9) ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001 (Student's t-test in (G) and One-way ANOVA in (D–F)).

Farzaneh Motafeghi and colleagues examined ARA290 in PC12 cells exposed to cadmium. Cell viability was evaluated by MTT assay, DNA damage by comet assay, oxidative-stress markers by measurements of ROS, MDA, GSH, TAC, and SOD activity, and apoptosis by TUNEL staining. Compared with cadmium-exposed controls, the authors reported higher cell viability, lower DNA damage, lower ROS and MDA, higher GSH, TAC, and SOD activity, fewer TUNEL-positive cells, and lower TNF-alpha, IL-1beta, and IL-6 measurements in ARA290-pretreated cells.[4] These findings were obtained in a cultured-cell model.

Guanglei Xu and colleagues established chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) mouse models and compared ARA290, fluoxetine, and control groups. The investigators measured behavioral endpoints together with peripheral blood, bone-marrow and meningeal myeloid-cell populations, and microglial activation. The authors reported differences in stress-associated behavioral measures and in the frequencies or numbers of CD11b+Ly6Ghi neutrophils and CD11b+Ly6Chi monocytes in the ARA290 groups, while effects on peripheral red-cell measures were described as marginal.[5]

Fig3. Bone-marrow erythroid and myeloid-cell measurements reported in the CUMS mouse study comparing control, stress, fluoxetine, and ARA290 groups.[5]

(A) Representative gating strategy. (B) Frequency and number of Ter119+ or CD71+ erythroid cells. (C) Frequency and number of CD45+CD11b+ myeloid cells. (D) Frequency and number of CD11b+CD11c-Ly6Ghi neutrophils, CD11b+CD11c-Ly6Chi monocytes, and CD11b+CD11c+ conventional dendritic cells (cDCs). Statistical values are reported in the source publication.[5]
Alay Nanavati and colleagues reported an earlier conference study in 18-month-old male Fischer 344 × Brown Norway rats assigned to ARA290 or saline groups. Longitudinal measurements included body weight, echocardiography, electrocardiography, and a frailty index. The authors reported group differences in age-related changes in basal heart rate, autonomic modulation, ejection fraction, body weight, and frailty measurements over the study period.[6] Because this report was published as a conference abstract, the available methodological and outcome detail is more limited than in the later full-length publication.[2]

Suri Gime and colleagues reported a small conference study involving nine TGAC8+ mice assigned to an ARA290 group (n = 5) or saline group (n = 4). Echocardiographic measurements of ejection fraction, fractional shortening, and stroke volume were followed over seven months. The authors reported significant group-by-time interactions for these systolic measurements, while no significant between-group differences were present at baseline.[7] The small sample size and abstract-only format limit the amount of information available for interpretation.

Research Limitations

The studies summarized above use different experimental systems, including cultured PC12 cells, rat nerve-injury models, chronic-stress mouse models, aging rat cohorts, and a small transgenic mouse study. Results from these systems are not directly interchangeable. Species, tissue environment, experimental exposure, study duration, and endpoint selection may all influence the observations reported, and preclinical findings cannot by themselves establish clinical safety or efficacy.[2-7]

Mechanistic interpretation also varies among the cited studies. ARA290 is commonly discussed in relation to erythropoietin-receptor and beta-common-receptor (CD131) signaling, while individual experiments examine different downstream pathways, including NLRP3, NF-kB, oxidative-stress, inflammatory-cell, and beta-common-receptor-associated responses.[1,3,5,8] These findings should be interpreted within the model and methods used in each publication rather than as evidence of a single mechanism across all tissues or conditions.

COCER Peptides provides ARA290 solely as a laboratory research material. It is not intended for human or veterinary use, administration, diagnosis, treatment, prevention, or any other clinical application. The research described on this page summarizes findings reported in third-party publications and does not represent a statement of clinical safety or efficacy for any COCER Peptides material.

▎Relevant Citations

References

[1] Dahan A, Brines M, Niesters M, et al. Targeting the innate repair receptor to treat neuropathy[J]. PAIN Reports, 2016,1(1):e566.

DOI:10.1097/pr9.0000000000000566.

[2] Winicki N M, Nanavati A P, Morrell C H, et al. A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan[J]. Frontiers in Cardiovascular Medicine, 2023,9:1096887.

DOI:10.3389/fcvm.2022.1096887.

[3] 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[J]. European Journal of Pharmacology, 2025,997:177610.

DOI:10.1016/j.ejphar.2025.177610.

[4] Motafeghi F, Fakhri B M S, Ghassemi Barghi N. Mechanisms of ARA290 in counteracting cadmium-triggered neurotoxicity in PC12 cells[J]. Toxicology Research, 2025,14(1):tfaf023.

DOI:10.1093/toxres/tfaf023.

[5] Xu G, Zou T, Deng L, et al. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Chronic Stress-Induced Depression-Like Behavior and Inflammation in Mice[J]. Frontiers in Pharmacology, 2022,13:896601.

DOI:10.3389/fphar.2022.896601.

[6] Nanavati A, Moen J, Axsom J, et al. ARA290, A Small Non-Hematopoietic Peptide Derived From Erythropoietin, Prolongs Healthspan And Attenuates Age-Associated Declines In The Heart's Structure And Function[J]. The FASEB Journal, 2018,32(S1):lb288.

DOI:10.1096/fasebj.2018.32.1_supplement.lb288.

[7] Gime S, Winicki N, Ahmet I, et al. Abstract Mo112: ARA290, a small peptide non-erythropoietic Erythropoietin derivative, ameliorates heart functional deterioration in a chronic cardiac stress model[J]. Circulation Research, 2024,135(Suppl 1):AMo112.

DOI:10.1161/res.135.suppl_1.mo112.

[8] Wang R L, Yang Z H, Huang Y Y, et al. Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the beta-common receptor in mice with cerebral ischemic stroke[J]. CNS Neuroscience & Therapeutics, 2024,30(3):e14676.

DOI:10.1111/cns.14676.

[9] PubChem. Cibinetide. PubChem CID 91810664. National Center for Biotechnology Information.

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