ARA290
Published research and evidence base
ARA290 (cibinetide) is an 11-amino-acid non-erythropoietic peptide engineered from the helix B domain of erythropoietin, designed to activate the innate repair receptor (an EPO receptor/CD131 heteromer) without stimulating erythropoiesis. Of the compounds in this category it has the most developed human evidence: multiple completed randomised placebo-controlled phase 2 trials in sarcoidosis-associated small fibre neuropathy, type 2 diabetes with painful neuropathy, and diabetic macular edema. Results have generally shown improvement in patient-reported neuropathic symptoms and in corneal nerve fibre measures, but no regulatory approval has followed and no phase 3 programme has reported.
- Studies cited
- 15
- Published 2023+
- 7
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- innate repair receptor / EPOR-CD131 heteroreceptor
- small fibre neuropathy and corneal nerve fibre density
- neuropathic pain and allodynia
- anti-inflammatory and monocyte modulation
- non-erythropoietic tissue protection
- metabolic control and islet protection
Compound identifiers
- CAS
- 1208243-50-8
- PubChem
- 91810664
What ARA290 is, chemically.
- Molecular formula
- C51H84N16O21
- Molecular weight
- 1257.3 g/mol
- CAS number
- 1208243-50-8
- PubChem CID
- 91810664
Cibinetide, ARA-290, pHBSP peptide
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
15 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Human clinical2020
A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema
Lois N, et al. · J Clin Med · phase 2 trial; treatment-naive patients with central retinal thickness above 400 um, self-administered cibinetide 4 mg/day subcutaneously for 12 weeks
The trial measured change from baseline to week 12 in best corrected visual acuity, central retinal thickness and central retinal sensitivity in diabetic macular edema.
- 02Human clinical2017
Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain
Culver DA, et al. · Invest Ophthalmol Vis Sci · phase 2b, 28-day, multicentre randomised trial; 64 subjects with sarcoidosis-associated small nerve fibre loss and neuropathic pain, corneal confocal microscopy endpoints
The trial assessed cibinetide's effect on corneal nerve fibre area and regenerating GAP-43-positive intraepidermal fibres as surrogate disease-modification endpoints alongside pain severity. This is the largest randomised dataset for the compound.
- 03Human clinical2015
ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes
Brines M, et al. · Mol Med · phase 2 controlled clinical trial in subjects with type 2 diabetes and painful neuropathy
ARA 290 was associated with improvements in metabolic control and in neuropathic symptoms in patients with type 2 diabetes, without the hematopoietic effects that limit erythropoietin.
- 04Human clinical2013
ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density
Dahan A, et al. · Mol Med · randomised controlled trial in sarcoidosis patients with small nerve fibre loss and damage
ARA 290 improved patient-reported symptoms of small nerve fibre loss and increased corneal nerve fibre density relative to control.
- 05Human clinical2012
Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study
Heij L, et al. · Mol Med · double-blind, placebo-controlled exploratory trial; 22 patients with sarcoidosis and small fibre neuropathy symptoms, intravenous dosing three times weekly
The pilot trial reported on the safety of ARA 290 and its effect on small fibre neuropathy symptoms in sarcoidosis, following preclinical evidence of reduced allodynia.
- 06Animal in vivo2026
Immunometabolic dysregulation drives selective executive cognitive dysfunction in male db/db mice
Alasousi D, et al. · Neurobiol Dis · male db/db mice and db/m lean controls on a touchscreen operant platform (pairwise visual discrimination and reversal learning), with glucose and insulin tolerance testing, flow cytometry and RNA-seq; ARA 290 treatment arm
Db/db mice showed intact associative learning but impaired cognitive flexibility during reversal learning. ARA 290 treatment improved insulin sensitivity and altered circulating immune cell populations in these mice.
- 07Animal in vivo2025
ARA290 Attenuates Apical Periodontitis via SIRT1/NF-kappaB/IL-1beta Pathway Modulation
Wang Y, et al. · Int Dent J · in vivo apical periodontitis models with macrophage pro-inflammatory response assays
ARA290 reduced macrophage pro-inflammatory responses in apical periodontitis, with the protective effect attributed to modulation of SIRT1/NF-kappaB/IL-1beta signalling in periapical lesions.
- 08Animal in vivo2025
ARA290, an alternative of erythropoietin, inhibits activation of NLRP3 inflammasome in schwann cells after sciatic nerve injury
Liu G, et al. · Eur J Pharmacol · rat sciatic nerve crush injury with Schwann cell analysis
Both erythropoietin and ARA290 inhibited the early inflammatory response and promoted functional recovery after sciatic nerve crush in rats, with suppression of NLRP3 inflammasome activation in Schwann cells.
- 09Animal in vivo2024
Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the beta-common receptor in mice with cerebral ischemic stroke
Wang RL, et al. · CNS Neurosci Ther · male C57BL/6J mice undergoing middle cerebral artery occlusion and reperfusion; neurological function tests, TTC staining and apoptosis immunofluorescence
ARA290 reduced cerebral infarct volume and neuronal apoptosis and improved neurological scores after middle cerebral artery occlusion, with the effect dependent on the beta-common receptor.
- 10Animal in vivo2022
A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan
Winicki NM, et al. · Front Cardiovasc Med · aged rodent model of age-associated cardiac inflammation and functional decline treated with ARA290
ARA290 reduced cardiac inflammation and fibrosis, attenuated age-associated declines in heart function and prolonged healthspan in the treated animals.
- 11Animal in vivo2011
ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain: an experimental study in rats and beta-common receptor knockout mice
Swartjes M, et al. · Anesthesiology · spared nerve injury model of neuropathic pain in rats and in mice lacking the beta-common receptor
ARA290 produced long-term relief of tactile and cold allodynia in rats, and the absence of effect in beta-common receptor knockout mice established that the receptor complex mediates the analgesic action. This is the foundational mechanism paper.
- 12In vitro2025
Mechanisms of ARA290 in counteracting cadmium-triggered neurotoxicity in PC12 cells
Motafeghi F, et al. · Toxicol Res (Camb) · cadmium-exposed PC12 neuronal cells treated with ARA290
ARA290 counteracted cadmium-induced neurotoxicity in PC12 cells through anti-inflammatory, anti-apoptotic and antioxidant mechanisms attributed to selective innate repair receptor activation.
- 13In vitro2023
Mechanistic Approach for Protective Effect of ARA290, a Specific Ligand for the Erythropoietin/CD131 Heteroreceptor, against Cisplatin-Induced Nephrotoxicity, the Involvement of Apoptosis and Inflammation Pathways
Ghassemi-Barghi N, et al. · Inflammation · HEK-293 and ACHN renal cell lines pretreated with ARA290 (50-400 nM) before cisplatin (2.5 uM)
ARA290 pretreatment reduced cisplatin-induced cytotoxicity, genotoxicity and oxidative stress in renal cell lines, with changes in apoptosis and inflammation pathway markers.
- 14In vitro2021
Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation
Yao M, et al. · Cell Transplant · isolated human pancreatic islets cultured with pro-inflammatory cytokines for 18 hours with or without cibinetide, plus instant blood-mediated inflammatory reaction assays
Cibinetide preserved ATP content and protected isolated human islets under cytokine stress and modulated the instant blood-mediated inflammatory reaction relevant to intraportal islet transplantation.
- 15Review2025
Phase-targeted erythropoietin derivatives for traumatic brain injury: bridging mechanisms to precision therapy
Sun Y, et al. · Front Neurol · review integrating structural biology, pharmacology and translational data on four engineered erythropoietin derivatives across the traumatic brain injury timeline
The review argued that recombinant erythropoietin limits secondary damage in animals but that its erythropoietic and thrombotic liabilities stalled clinical adoption, positioning non-erythropoietic derivatives such as ARA290 for phase-targeted use.
What this evidence does not establish.
Despite more than a decade of phase 2 work, no phase 3 trial has reported and cibinetide has no regulatory approval in any jurisdiction; the human trials are small, short (28 days to 12 weeks) and concentrated in sarcoidosis and diabetic neuropathy rather than musculoskeletal recovery. There is no published human study of ARA290 for tendon, muscle or exercise-related recovery, which is how it is marketed in this category.
Common questions about the research.
- What is ARA290?
ARA290, also called cibinetide, is an 11-amino-acid peptide engineered from the helix B region of erythropoietin. It was designed to retain the tissue-protective signalling of the parent hormone without its erythropoietic activity.
- What is the innate repair receptor?
The literature describes it as a heteromeric receptor complex formed from the erythropoietin receptor and the beta-common receptor subunit (CD131). It is reported as being expressed on injured or metabolically stressed tissue rather than throughout the body, which is why ARA290 is characterised as acting at sites of injury.
- Does it raise haemoglobin like erythropoietin?
The design intent was specifically to avoid that. The peptide omits the erythropoietin residues associated with red blood cell production, and the published studies report no erythropoietic effect while assessing tissue-protective end points.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.