Section 01
What it's used for
No Stroke or TBI Studies Exist
No published study has tested Epobis in stroke or brain injury; only two lab papers exist, both from one Copenhagen research group. In cell culture, it protected neurons from cell death and promoted nerve growth. There is no human data.
▸Clinical wording
No published study has tested Epobis in a stroke or traumatic brain injury model; a PubMed search for "Epobis" returns only two primary reports, both from the same University of Copenhagen laboratory. What has been shown is cell-culture neuroprotection: Epobis binds the erythropoietin receptor and, in an EPOR-expression-dependent manner, induces neurite outgrowth from primary neurons and protects hippocampal neurons against kainate-induced death and cerebellar granule neurons against death from potassium deprivation. A later study added neurite outgrowth from primary rat motoneurons, maximal at 0.33 µM. All neuroprotection evidence is therefore in vitro or from the autoimmune-inflammation model described below; there is no human data of any kind.
Cardioprotection Claim Unproven
Neither published Epobis paper tested heart cells or heart models. Cardioprotection data often cited for this class comes from a different peptide (HBSP), from a different part of the EPO protein — results that don't transfer to Epobis.
▸Clinical wording
This direction is described without published Epobis findings behind it: neither of the two indexed Epobis papers used a cardiac model, cardiomyocytes or any cardiovascular endpoint. The cardioprotection data usually cited for "non-erythropoietic EPO peptides" belong to a different molecule — the helix B surface peptide (HBSP, QEQLERALNSS), derived from the aqueous face of EPO helix B, which reduced TNF-α-induced apoptosis in cultured neonatal rat cardiomyocytes and in a hamster dilated-cardiomyopathy model without stimulating erythropoiesis. Epobis is derived from a different region of EPO (binding site 1, residues 63–80), so the HBSP results cannot be transferred to it.
Anti-Inflammatory Effects in Rats
In cell culture, Epobis lowered inflammatory signaling from immune cells. In a rat multiple-sclerosis model, a 5-day course delayed symptom onset, significant only at day 2 (p<0.05), but didn't change weight loss or survival. Unreplicated.
▸Clinical wording
In cell culture, Epobis reduced TNF secretion from the AMJ2-C8 mouse macrophage line and, at 0.9 µM but not at 8.1 µM, from LPS-stimulated primary rat microglia. In vivo, female Lewis rats with experimental autoimmune encephalomyelitis (a multiple-sclerosis model) given 10 mg/kg subcutaneously daily for five days showed a delay in clinical signs that reached significance only at day 2 after onset (p < 0.05); weight loss, survival and activated-microglia counts did not differ from vehicle controls. This is one animal experiment from a single laboratory with a modest, short-lived effect, and it has not been replicated.
Doesn't Boost Red Blood Cells
In mice, a 5-week course of Epobis did not raise red blood cell counts, unlike regular EPO at the same dose — its best-supported finding. The "tissue repair" idea rests only on cell-culture nerve studies; no organ-repair study exists.
▸Clinical wording
The "without erythropoiesis" half of this claim is the best-supported Epobis finding: female C57BL/6J mice given 10 mg/kg subcutaneously twice weekly for five weeks showed no statistically significant increase in haematocrit or haemoglobin at any time point, whereas recombinant EPO at the same dose did. The "tissue repair" half rests only on neuronal assays in culture — neurite outgrowth and survival of stressed hippocampal, cerebellar and motor neurons. No wound-healing, kidney, liver or other organ-repair study with Epobis has been published, so the compound is better described as non-erythropoietic than as a demonstrated repair agent.
Memory Test in Healthy Rats
In rats, a single dose of Epobis reached the brain within hours after an injection under the skin. In one memory test, treated rats showed better social recognition at 73 hours (p<0.018), but not at 1 hour. One rat study; no human data.
▸Clinical wording
Biotinylated Epobis given as a single 10 mg/kg subcutaneous dose to adult Wistar rats appeared in plasma within 15 minutes, peaked at about 2 hours, remained detectable at 24 hours, and was found in cerebrospinal fluid at 2 hours with a plasma-to-CSF ratio of roughly 20:1 — evidence that the peptide reaches the central nervous system after peripheral dosing. In a social-recognition test the same single dose produced no change at 1 hour but a significant change in recognition ratio at 73 hours (p < 0.018), which the authors interpreted as improved social memory three days after administration. This is a single behavioural experiment in healthy rats from the originating group, and no human cognitive data exist.
Section 02
Mechanism of Action
A copied fragment of a blood hormone
- Epobis reproduces an eighteen-residue stretch of human erythropoietin, part of its high-affinity receptor contact site.
- It is presented as a four-armed branched molecule rather than a single straight chain.
- Laboratory binding measurement showed specific attachment to the receptor at around 60 nanomolar.
- Both reports propose the four-armed display forces two receptor chains together, which one contact alone could not.
▸Clinical wording
EPO binding Site 1 mimicry at the erythropoietin receptor
Epobis is a synthetic peptide whose sequence, NENITVPDTKVNFYAWKR, reproduces residues 63-80 of human erythropoietin, part of the high-affinity binding Site 1 identified in the crystal structure of the EPO:EPOR2 complex. It is presented as a dendrimeric tetramer rather than a linear monomer. Surface plasmon resonance measured specific binding to the EPO receptor with an apparent KD near 60 nM. Both primary reports propose that the tetrameric display promotes EPOR dimerisation by imposing the conformational change that ligand occupancy of Site 1 normally produces, since one Site 1 contact alone would not bridge two receptor chains.
Growing nerve fibres through one receptor
- In nerve cell cultures Epobis triggers fibre outgrowth only where the receptor is expressed.
- That receptor dependence is the main evidence it is not acting non-specifically.
- In rat motor neurons the concentration response is bell-shaped, peaking near 0.33 micromolar.
- Neither paper reports three other common signalling routes, and one alternative receptor was never tested.
▸Clinical wording
EPOR-dependent neuritogenesis and STAT5 activation
In primary neuronal cultures Epobis induces neurite outgrowth, and the response tracks EPOR expression: it is absent where the receptor is not expressed, which is the main evidence that the peptide acts through EPOR rather than non-specifically. In primary rat motor neurons the concentration-response is bell-shaped, with the maximum near 0.33 µM. Downstream, Epobis promotes activation of the transcription factor STAT5. Neither Epobis paper reports PI3K/Akt, ERK1/2 or NF-κB data, and the beta-common receptor (CD131) that carries tissue protection for other EPO derivatives has not been tested with this peptide.
Keeping stressed nerve cells alive in dishes
- Two rodent culture models of nerve cell death were used to test survival.
- Hippocampal cells were challenged with an over-stimulating glutamate agent, and cerebellar cells lost their support signal.
- In both settings Epobis increased the share of nerve cells that survived.
- The effect is pro-survival rather than regenerative, and no living-animal injury model has been reported.
▸Clinical wording
Neuronal survival under excitotoxic and osmotic stress
Survival was probed in two rodent primary culture models of neuronal death. Hippocampal neurons were challenged with kainate, an excitotoxic glutamate-receptor agonist, and cerebellar neurons were switched to low-potassium medium, which removes the depolarising trophic support these cells depend on. In both settings Epobis increased the fraction of surviving neurons. The effect is described as pro-survival rather than regenerative, and it was measured only in culture: no ischaemia or trauma model in a living animal has been reported for this peptide.
Quietening inflammatory immune cells
- Epobis lowered an inflammatory messenger released by a macrophage line and by rat brain immune cells.
- Fluid from treated macrophages kept far more test cells alive than fluid from untreated ones.
- In rats with an autoimmune nerve disease, clinical scores were lower only shortly after symptoms began.
- The peptide delayed rather than prevented disease, and weight loss and survival were unchanged.
▸Clinical wording
Cytokine suppression in macrophages and microglia
Epobis reduced LPS-induced TNF secretion from an AMJ2-C8 macrophage line and from rat primary microglia at submicromolar concentrations. The reduction was functionally meaningful in a bystander assay: conditioned medium taken from Epobis-treated macrophages left L-cell viability near 68 percent against roughly 48 percent for medium from untreated cells. In female Lewis rats with experimental autoimmune encephalomyelitis, treated animals had lower clinical scores shortly after symptom onset, so the peptide delayed rather than prevented disease; weight loss and survival were unchanged.
Reaches the brain without boosting red cells
- Labelled Epobis injected under the skin of rats appeared in blood within fifteen minutes.
- A measurable fraction reached the fluid around the brain and spinal cord intact.
- Five weeks of repeated dosing in mice changed neither red cell fraction nor haemoglobin, unlike erythropoietin itself.
- In a rat social recognition test, performance was unchanged at one hour but better three days later.
▸Clinical wording
Central exposure uncoupled from erythropoiesis
Biotinylated Epobis given subcutaneously to Wistar rats appeared in plasma within 15 minutes and reached cerebrospinal fluid at about 0.2 µg/mL, a plasma-to-CSF ratio near 20 at two hours, so a measurable fraction crosses the blood-brain barrier intact. Over five weeks of repeated subcutaneous administration in C57BL/6J mice the peptide produced no statistically significant change in haematocrit or haemoglobin, while erythropoietin itself raised both. In a social recognition test in rats, recognition was unchanged at one hour but improved three days after administration.
Section 03
Biological Pathways
No data for this section yet.
Section 04
Dosage Information
EPO-derived cytoprotective peptide| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Subcutaneous — rat models | Rat model of multiple sclerosis; a memory test | 10 mg/kg daily for 5 days, plus one 10 mg/kg dose in the memory test — 700–900 mg for a 70–90 kg adult if carried across unchanged | Nobody scaled the animal dose to humans, so that gram-scale figure is arithmetic, not a dose. It delayed disease signs in rats; there is no human equivalent. |
| Subcutaneous — blood counts in mice | Five-week check for red-cell-raising activity | 10 mg/kg twice a week for 5 weeks; the share of red cells in blood (haematocrit) and haemoglobin were unchanged at every weekly check | That experiment answered one question — Epobis does not raise red cells — and no other. No toxicology, organ-safety or repeat-dose study has been published. |
| Subcutaneous — blood levels in rats | One time-course in rats; nothing in humans | One 10 mg/kg dose in rats: in blood at 15 min, peak near 2 h, still there at 24 h; spinal fluid held 0.2 µg/mL at 2 h, 20× lower | Epobis has never been given to a human being. Even in rats nobody worked out how fast it leaves the body, and no human study exists. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Lyophilised powder
The powder is kept sealed and away from moisture: the reagent catalogue gives 2 years at −80 °C and 1 year at −20 °C. Solubility is at least 50 mg/ml in water and 4 mg/ml in DMSO with sonication. The peptide is synthesised as a tetrameric dendrimer rather than a single chain.
After reconstitution
The stock solution is held under the same sealed, moisture-free conditions: up to 6 months at −80 °C or up to 1 month at −20 °C.
Section 07
Side Effects & Precautions
Epobis has never been given to a human: no trials are registered and no human study exists in the literature. The record is two preclinical papers from one research group, with no independent replication. The only safety-relevant measurement: mice tracked weekly for five weeks showed no rise in hematocrit or hemoglobin on Epobis, but this was not a toxicity study — it tracked no mortality, weight, blood chemistry, or organ tissue. No toxicology study exists, and no data exist for pregnancy, children, or liver or kidney impairment. Epobis is structurally different from ARA-290, so ARA-290's safety data do not apply to it.
Section 08
Regulatory Status
It is a laboratory research reagent with no approval, no clinical trial and no authorised use outside animal and cell studies.
FDA / United States
Not approved; research use only
Epobis has no FDA marketing approval, and no drug application has ever been filed for it. Chemical suppliers such as MedChemExpress and TargetMol sell it strictly as a research reagent, stating explicitly that it is not intended for human use.
EMA / European Union
No authorisation of any kind exists
Epobis has not been assessed by the EMA or by any national EU regulator, either as a medicine or under any other regulated category.
Clinical trials
None have ever been conducted
Published data come only from rodent and cell-culture studies of this engineered erythropoietin-receptor agonist, showing anti-inflammatory and memory effects without raising haemoglobin. No human trial of Epobis has been registered or run.
WADA
Not named on the list; S0 applies by definition
Epobis is not listed by name on the WADA Prohibited List, but as an unapproved pharmacological substance with no governmental approval for human therapeutic use, it meets the definition of category S0 (Non-Approved Substances), which covers compounds not addressed elsewhere on the List.
A research-chemical listing is not a safety or purity guarantee, and it is not a step toward approval. Regulatory status differs by jurisdiction and changes over time — check current official sources before relying on any of this.
Section 09
Research Studies
- [1]A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth and promotes neuronal survivalPankratova S, Gu B, Kiryushko D, Korshunova I, Køhler LB, Rathje M, Bock E, Berezin V. · Journal of Neurochemistry · 2012
- [2]Epobis is a Nonerythropoietic and Neuroprotective Agonist of the Erythropoietin Receptor with Anti-Inflammatory and Memory Enhancing EffectsDmytriyeva O, Pankratova S, Korshunova I, Walmod PS. · Mediators of Inflammation · 2016
- [3]Second-generation non-hematopoietic erythropoietin-derived peptide for neuroprotectionCho B, Yoo SJ, Kim SY, Lee CH, Lee YI, Lee SR, Moon C. · Redox Biology · 2022
Section 10
Frequently Asked Questions
Epobis is a synthetic peptide built from a fragment of human erythropoietin — residues 63 to 80, presented as a four-armed dendrimer rather than a single chain. It binds the erythropoietin receptor and activates it without triggering the red-blood-cell-producing effect of natural EPO. Only two primary research papers on it exist, both from the same University of Copenhagen laboratory, covering cell-culture and rodent experiments; there is no published cardioprotection data for Epobis itself, despite that direction sometimes being described for the molecule.
No. Every published finding on Epobis comes from cell culture — neurons, macrophages, microglia — or from rats and mice: a multiple-sclerosis rat model, a blood-count study in mice, and a single pharmacokinetic and behavioral experiment in rats. No human trial, safety study, or dosing study of any kind has been conducted.
The published evidence is preliminary and comes from a single lab. In cell culture Epobis protects stressed neurons and reduces inflammatory TNF release from macrophages and microglia. In one rat model of multiple sclerosis it modestly delayed disease onset, an effect that reached statistical significance only on a single day and has not been replicated. A one-off memory experiment in healthy rats found improved social recognition three days after a single dose. None of this has been tested further, and there is no human efficacy data at all.
No — that is its defining feature. In mice given 10 mg/kg subcutaneously twice a week for five weeks, haematocrit and haemoglobin stayed unchanged at every check, whereas the same dose of recombinant EPO raised them. This is the best-supported finding for Epobis: it activates the erythropoietin receptor without the blood-thickening effect that limits therapeutic use of EPO itself.
Rat and mouse studies used 10 mg/kg subcutaneously — daily for five days in the multiple-sclerosis model, twice weekly for five weeks in the blood-count study, or as a single dose in the pharmacokinetic and memory experiments. Scaled arithmetically to a 70-90 kg adult that would be 700 to 900 mg, but nobody has actually scaled or tested a human dose; no dose-finding, toxicology, or repeat-dose study exists beyond these single animal experiments.
There is no regulatory status on record for Epobis — it has not been reviewed by the FDA, EMA, or any other regulator identified, and no WADA listing was found for it either. It exists only as a research compound described in two published papers, not as a developed or marketed substance, so there is no ruling to point to either way.
As a lyophilised powder it is rated for 2 years at -80 °C or 1 year at -20 °C, sealed and protected from moisture — only freezer temperatures are given, with no room-temperature or 2-8 °C refrigerator figures reported. Once reconstituted, the stock solution is rated for up to 6 months at -80 °C or 1 month at -20 °C.