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Erythropoietin

EPO · Epoetin · Procrit · Epogen

Pituitary & Trophic HormonesApproved
MW
848g/mol
Formula
C42H73NO16

Erythropoietin (Epo) is a glycoprotein hormone primarily produced in the kidneys, with additional synthesis occurring in the liver. Researchers primarily study Epo for its critical role in stimulating the production of red blood cells (RBCs) and its implications in conditions such as anemia and hypoxia. Key findings indicate that Epo secretion is stimulated by low oxygen levels, and its receptor is expressed in various tissues, including the central nervous system, where it may exert neuroprotective effects. Clinical evidence suggests that recombinant forms of Epo have been misused in sports for performance enhancement, leading to the development of sophisticated detection methods. Current research continues to explore Epo's multifaceted roles in erythropoiesis and potential therapeutic applications beyond hematopoiesis, highlighting its significance in both clinical and athletic contexts.

Overview

Übersicht

Erythropoietin (EPO) is a glycoprotein hormone primarily produced in the kidneys, with additional production occurring in the liver. It is part of the pituitary and trophic hormone category. Endogenously, it is synthesized by peritubular cells in the renal cortex and hepatocytes in the liver. Chemically, EPO is characterized by its glycosylation sites, with three N-glycosylation and one O-glycosylation site, contributing to its stability and function. Researchers have found that EPO plays a critical role in erythropoiesis, stimulating the production and differentiation of red blood cells, thereby enhancing tissue oxygenation. This property has been exploited in both therapeutic and illicit contexts, such as treating anemia and in sports doping. EPO also exhibits potential neuroprotective effects, as its receptors are expressed in the central nervous system, influencing neurogenesis and recovery from hypoxic injury. The mechanism of action of EPO involves binding to the erythropoietin receptor (Epo-R), a multimeric protein, which activates intracellular signaling pathways that promote erythrocyte proliferation. Recombinant forms of EPO, such as epoetin and darbepoetin, mimic these effects but differ in glycosylation patterns, affecting their pharmacokinetics. Pharmacokinetic studies indicate that recombinant EPO has a plasma half-life of over 24 hours when administered subcutaneously, with a bioavailability of 20-30%. Darbepoetin, a longer-acting analogue, has a half-life of approximately 48 hours. Clinically, EPO is used to manage anemia in patients with chronic kidney disease and chemotherapy-induced anemia. It is regulated by anti-doping agencies due to its misuse in sports, and its use is closely monitored in medical settings to mitigate risks such as hypertension and thrombotic events.

Chemical profile

Chemische Struktur

Chemical structure of Erythropoietin
FormelC42H73NO16
Molekulargewicht848g/mol
CAS-Nummer113427-24-0
PubChem CID92043599
Mechanism

Wirkmechanismus

Erythropoietin acts on the erythropoietin receptor (Epo-R), initiating a cascade that promotes erythrocyte proliferation and differentiation. This receptor-mediated activation involves intracellular signaling pathways crucial for red blood cell production and tissue oxygenation.

Mechanism

Signalweg

Erythropoietin (Epo) primarily acts through the erythropoietin receptor (Epo-R), a multimeric protein that activates the JAK2/STAT5 signaling pathway upon Epo binding. This activation promotes erythropoiesis by stimulating the proliferation and differentiation of erythroid progenitor cells in the bone marrow, leading to increased red blood cell production and enhanced tissue oxygenation. While the core mechanism is well-established, the complete structural understanding of the Epo-R and potential accessory chains remains to be fully elucidated.

Half-Life & Pharmacokinetics

ENEndogenous

Circulating half-life ~5-9 hours

SCSubcutaneous

Bioavailability ~20-30%, half-life >24 hours

IVIntravenous

Half-life ~4-13 hours

POOral

Poor bioavailability due to first-pass metabolism

Darbepoetin has a longer half-life (~48 hours) compared to epoetin due to additional glycosylation.

Storage

Temperature

Refrigerate at 2-8C

Light

Protect from light

Form

Aqueous solution: use within specified time after opening

Notes

Avoid freezing; follow specific storage instructions for stability.

Solubility

Löslichkeit

Erythropoietin is soluble in aqueous solutions, suitable for parenteral formulations.

Legal Status

🇩🇪DE

Prescription only (verschreibungspflichtig); not a controlled substance under BtMG.

🇺🇸US

FDA approved for specific anemias; prescription required.

🇦🇺AU

TGA Schedule 4 (prescription only medicine).

🇬🇧UK

Prescription only medicine (POM); regulated by MHRA.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Open Questions

Offene Forschungsfragen

Current evidence is limited regarding the long-term effects and safety profiles of erythropoietin (Epo) and its analogs in diverse populations, particularly in pediatric and elderly patients. Further research is needed to clarify the mechanisms underlying Epo's neuroprotective effects in the central nervous system, as well as to establish standardized protocols for its use in treating hypoxia-related conditions. Additionally, larger randomized controlled trials (RCTs) are necessary to assess the efficacy and safety of various Epo formulations in the management of anemia across different clinical settings, including cancer and chronic kidney disease.

64 Research Publications

3,844

Total Citations

7

Human/RCT

4.4

Avg. Influence

2019

Latest

Sort
Filter
#01

New avenues of exploration for erythropoietin.

ReviewInfluence20.0
536
The review highlighted erythropoietin's emerging role as a cytoprotective agent in various non-hematopoietic disorders, including cerebral ischemia and myocardial infarction.
#02

The non-haematopoietic biological effects of erythropoietin.

ReviewInfluence13.0
354
Researchers observed that erythropoietin signaling has significant biological effects beyond hematopoiesis, including roles in angiogenesis and tissue protection in various organs.
#03

Erythropoietins: a common mechanism of action.

ReviewInfluence18.0
259
Researchers observed that erythropoiesis-stimulating agents act through multiple signaling pathways to enhance red blood cell production, with the duration of EPO concentration being a key factor in response.
#04

Role of erythropoietin in the brain.

ReviewInfluence14.0
234
Researchers observed that erythropoietin plays a significant role in brain development and neuroprotection, with potential therapeutic implications for ischemic and traumatic brain injuries.
#05

Physiology and pharmacology of erythropoietin.

ReviewInfluence13.0
226
Researchers observed that erythropoietin (EPO) is essential for erythropoiesis and has multi-tissue effects, influencing various physiological responses to ischemic stress.
#06

The erythropoietin receptor and its expression in tumor cells and other tissues.

ReviewInfluence5.0
203
Researchers observed that erythropoietin and its receptor are expressed in various nonhematopoietic tissues, including tumors, and while its effects on tumor growth are inconclusive, it may reduce hypoxia-related complications in cancer.
#07

The Many Facets of Erythropoietin Physiologic and Metabolic Response.

AnimalInfluence6.0
169
Researchers observed that erythropoietin (EPO) influences metabolic responses and may protect against inflammation in white adipose tissue, with gender-specific effects noted in mice.
#08

Hyporesponsiveness to recombinant human erythropoietin.

ReviewInfluence5.0
151
Researchers observed that multiple factors, including iron deficiency and inflammation, contribute to hyporesponsiveness to recombinant human erythropoietin in patients with renal failure.
#09

Clinical pharmacokinetics of epoetin (recombinant human erythropoietin).

ReviewInfluence4.0
127
The study demonstrated that various administration routes of epoetin show distinct pharmacokinetic profiles, influencing its therapeutic application in renal anemia management.
#10

Erythropoietin and Its Angiogenic Activity.

ReviewInfluence2.0
108
Researchers observed that erythropoietin exhibits angiogenic activity in various tissues, highlighting its potential roles in both promoting and protecting against ischemic damage.

Clinical Trials (41)

Preclinical
Phase I
Phase II
Phase III
Approved

41

Total Trials

11,257

Total Enrolled

A Study to Evaluate Whether Correction of Anemia Using Recombinant Human Erythropoietin Reduces the Progression of Atherosclerosis and Cardiac Hypertrophy in Pre-dialysis Chronic Kidney Disease Patients

NCT00563355COMPLETED
Sponsor

Hospital Authority, Hong Kong

Enrollment

66

Started

2001

Primary outcome

endothelial function and atherosclerosis

Chronic DiseaseKidney DiseasesCardiovascular Diseases

Effectiveness of a Biosimilar Epoetin Alfa in Stable 'End Stage Renal Failure'

Sponsor

Penang Hospital, Malaysia

Enrollment

44

Started

2015

Primary outcome

Mean change in haemoglobin levels

End Stage Renal FailureAnaemia

Identification of New Serum Markers for Detection of Abuse With Erythropoietin

NCT01320449COMPLETED
Sponsor

University of Aarhus

Enrollment

35

Started

2011

Primary outcome

Changes in serum protein isoforms measured by proteomics

Substance Abuse Problem

Tracing Changed Production of Red Blood Cells

NCT05833477COMPLETED
Sponsor

University of Copenhagen

Enrollment

12

Started

2022

Primary outcome

Changes in CD71 expression

ErythrocytosisErythropoiesis Abnormal

Treatment With Erythropoietin and Cognition During Hypoglycaemia

NCT00615368COMPLETED
Sponsor

Hillerod Hospital, Denmark

Enrollment

11

Started

2008

Primary outcome

Cognitive function

Type 1 DiabetesHypoglycemia

A Double-Blind, Placebo-Controlled Study With Open-Label Follow-Up To Determine the Safety and Efficacy of r-HuEPO in AIDS Patients With Anemia Induced by Their Disease and AZT Therapy

NCT00002071COMPLETED
Sponsor

Ortho Pharmaceuticals

HIV InfectionsCytopenias

A Study of Methoxy Polyethylene Glycol-Epoetin Beta (Mircera) for the Treatment of Chronic Renal Anemia in Participants With Diabetic Nephropathy

NCT01191983Phase 4COMPLETED
Sponsor

Hoffmann-La Roche

Enrollment

102

Started

2010

Primary outcome

Mean time taken to achieve target hemoglobin (Hb) levels range (10-12 g/dL) During Efficacy Evaluation Period (EEP)

Anemia

A Study of NeoRecormon in Patients With Chronic Kidney Disease.

NCT00437723Phase 4COMPLETED
Sponsor

Hoffmann-La Roche

Enrollment

90

Primary outcome

Hb level, decline in renal function, 24h proteinuria, creatinine clearance.

Anemia

Viral Kinetics of Treatment With Peginterferon Alpha-2a, Ribavirin and Epoetin β in Patients Coinfected HCV/HIV

NCT00356486Phase 4COMPLETED
Sponsor

Germans Trias i Pujol Hospital

Enrollment

74

Started

2005

Primary outcome

Percentage of patients with undetectable RNA-HCV

HIV Infections

A Study of Subcutaneous Mircera, Versus no Erythropoiesis-Stimulating Agent (ESA) Therapy, in the Treatment of Anemia in Patients With Chronic Kidney Disease After Kidney Transplant

NCT00576602Phase 4TERMINATED
Sponsor

Hoffmann-La Roche

Enrollment

1

Started

2007

Primary outcome

Change in Hb concentration between baseline and efficacy evaluation period (EEP).

Anemia

Study to Evaluate Effectiveness of Aranesp®

NCT00117130Phase 4COMPLETED
Sponsor

Amgen

Primary outcome

Subject preference

Kidney Disease

Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Non-Dialysis (ASCEND-ND)

NCT02876835Phase 3COMPLETED
Sponsor

GlaxoSmithKline

Enrollment

3,872

Started

2016

Primary outcome

Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period (Non-inferiority Analysis)

Anaemia

Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy

NCT00858364Phase 3TERMINATED
Sponsor

Amgen

Enrollment

2,549

Started

2009

Primary outcome

Overall Survival (OS)

Non-Small Cell Lung CancerAnemiaCancerLung Cancer

The Clinical Evaluation of the Dose of Erythropoietins Trial

NCT00827021Phase 3COMPLETED
Sponsor

Giovanni FM Strippoli, MD

Enrollment

656

Started

2009

Primary outcome

TSAT (transferrin saturation), serum albumin, serum ferritin, serum transferrin, serum C reactive protein

Kidney Failure, Chronic

Efficacy of Epoetin Alfa Deep Tank in Treatment of Anemia in Patients With Chronic Kidney Disease Receiving Hemodialysis

NCT00146224Phase 3COMPLETED
Sponsor

Amgen

Enrollment

420

Started

2005

Primary outcome

Ratio of weekly dose at the evaluation period to the weekly dose at baseline

Nephrology

A Study to Determine Whether Epoetin Alfa Can Reduce the Need for Blood Transfusions in Patients During the Period of Time Around Major Orthopedic Surgery.

NCT00270088Phase 3COMPLETED
Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Enrollment

316

Started

1993

Primary outcome

Proportion of patients in each treatment group, overall, and within each baseline hemoglobin group requiring blood transfusion following major orthopedic surgery

AnemiaBlood TransfusionOrthopedic Procedures

A Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients With Anemia

NCT02952092Phase 3COMPLETED
Sponsor

Astellas Pharma Inc

Enrollment

303

Started

2016

Primary outcome

Change from baseline in the average hemoglobin (Hb)

Hemodialysis Chronic Kidney Disease Patients With Anemia

Efficacy Study of Erythropoietin After Revascularization in Myocardial Infarction (REVIVAL-3)

NCT00390832Phase 3COMPLETED
Sponsor

Deutsches Herzzentrum Muenchen

Enrollment

138

Started

2006

Primary outcome

Left ventricular ejection fraction measured by magnetic resonance imaging

Myocardial InfarctionAngioplasty, Transluminal, Percutaneous Coronary

A Study of Mircera in Hemoglobin Control of Patients Transitioning to Dialysis.

NCT00454246Phase 3TERMINATED
Sponsor

Hoffmann-La Roche

Enrollment

111

Started

2007

Primary outcome

Percentage of Patients Able to Maintain Hemoglobin (Hb) Within 10-12 g/dL

Anemia

Treatment of Optic Neuritis With Erythropoietin: a Randomised, Double-blind, Placebo-controlled Trial

NCT01962571Phase 3COMPLETED
Sponsor

University Eye Hospital, Freiburg

Enrollment

108

Started

2014

Primary outcome

Global retinal nerve fibre layer thickness (RNFLT-G)

Optic Neuritis

Clinical Efficacy of Two Erythropoietin Drug in Participants With Secondary Anemia to Chronic Kidney Disease.

NCT01695759Phase 3TERMINATED
Sponsor

Azidus Brasil

Enrollment

92

Started

2013

Primary outcome

Change of hemoglobin levels at correction phase (baseline vs end of treatment)

Chronic Kidney DiseaseAnemia

Decitabine for Poor Graft Function Post Allo-HSCT

NCT05907499Phase 3NOT_YET_RECRUITING
Sponsor

The First Affiliated Hospital of Soochow University

Enrollment

76

Started

2023

Primary outcome

The treatment response

Poor Graft Function

A Study of Recombinant Human Erythropoietin Beta (NeoRecormon) in Anemic Cancer Participants Treated With Chemotherapy

NCT02767765Phase 3COMPLETED
Sponsor

Hoffmann-La Roche

Enrollment

61

Started

2003

Primary outcome

Percentage of Participants With Response to Treatment

Anemia

Study of the Efficacy and Safety of Epoetin Alfa Administered Weekly in Patients With Gastric or Rectal Cancers Undergoing a Treatment Plan of Preoperative Chemotherapy and Radiation Therapy, Followed by Surgery

NCT00036400Phase 3COMPLETED
Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Enrollment

60

Started

2001

Primary outcome

Number of red blood cell transfusions

Stomach NeoplasmsRectal Neoplasms

An Efficacy and Safety Study for Epoetin Alfa (PROCRIT) in Cancer Patients Not Receiving Chemotherapy or Radiation

NCT00210587Phase 3COMPLETED
Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Enrollment

51

Started

2005

Primary outcome

Percent of patients that achieved a hematopoietic response, defined as a Hb increase >= 2 g/dL and/or Hb = 12 g/dL during the study independent of transfusion within 28 days

AnemiaNeoplasms

Topical Erythropoietin Hydrogel in Management of Oral Lichen Planus

NCT06135259Phase 3UNKNOWN
Sponsor

Ain Shams University

Enrollment

18

Started

2024

Primary outcome

Clinical Scoring

Oral Lichen Planus

Neuroprotective Role of Erythropoietin in Perinatal Asphyxia

NCT02002039Phase 2/3COMPLETED
Sponsor

Sheri Kashmir Institute of Medical Sciences

Enrollment

100

Started

2012

Primary outcome

Death or moderate or severe disability at 18-22 months of age

Perinatal Asphyxia

Clinical Study to Examine the Effects of Erythropoietin on Left Ventricular Function After Acute Myocardial Infarction

NCT00449488Phase 2COMPLETED
Sponsor

University Medical Center Groningen

Enrollment

529

Started

2007

Primary outcome

Left ventricular ejection fraction 6 weeks after primary PCI, measured with planar radionuclide ventriculography

Myocardial Infarction

Study to Develop a Screening Tool for Functional Capacity in Anemic Subjects With Nonmyeloid Malignancies Receiving Chemotherapy and Darbepoetin Alfa

NCT00540696Phase 2COMPLETED
Sponsor

Amgen

Enrollment

300

Started

2001

Primary outcome

Proportion of subjects whose baseline score on the subjective FCST correctly estimates the baseline MHST score

AnemiaNon-Myeloid Malignancies

Heart Failure and Anemia

NCT00049985Phase 2COMPLETED
Sponsor

Amgen

Enrollment

300

Started

2002

Primary outcome

Exercise tolerance

Heart FailureAnemia

A Study Comparing Two Different PROCRIT Doses to a Dose of ARANESP in Anemic Cancer Patients Receiving Chemotherapy

NCT00386152Phase 2TERMINATED
Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Enrollment

235

Started

2006

Primary outcome

Hemoglobin (Hb) Change From Baseline to Study Week 7

NeoplasmsAnemiaCancer

Darbepoetin in Neonatal Encephalopathy Trial

NCT04432662Phase 2UNKNOWN
Sponsor

Imperial College London

Enrollment

150

Started

2021

Primary outcome

Primary outcome measure (Mean (SD) of thalamic NAA level)

Neonatal Encephalopathy

Treatment of the Anemia of Myelodysplastic Syndromes by the Association of Epoetin Beta and All Trans Retinoic Acid

NCT00437450Phase 2UNKNOWN
Sponsor

Groupe Francophone des Myelodysplasies

Enrollment

99

Started

2004

Primary outcome

To evaluate the efficacy of association of Erythropoetin and ATRA in patients with low risk myelodysplastic syndromes

Anemia in Myelodysplastic Syndromes

Study of SSS06 for Chemotherapy-Induced Anemia in Non-Myeloid Malignancies

NCT06854276Phase 2NOT_YET_RECRUITING
Sponsor

Shenyang Sunshine Pharmaceutical Co., LTD.

Enrollment

80

Started

2025

Primary outcome

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) Events (NCI-CTCAE V5.0).

Chemotherapy-induced AnemiaNon-myeloid Malignancies

4 Week Switch Study in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease

NCT01587924Phase 2COMPLETED
Sponsor

GlaxoSmithKline

Enrollment

80

Started

2012

Primary outcome

Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment

Anaemia

A Study to Investigate the Neuroprotective Effect of PROCRIT (Epoetin Alfa) Versus Placebo in Cancer Patients Who Develop Chemotherapy-induced Peripheral Neuropathy

NCT00267007Phase 2TERMINATED
Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Enrollment

32

Started

2006

Primary outcome

The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 1) at Week 12.

Peripheral Neuropathy, Chemotherapy-induced

Randomized, Double-blind, Placebo-controlled Study to Assess Fatigue in Patients With ACD Due to RA Receiving PROCRIT

NCT00236678Phase 2TERMINATED
Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Enrollment

29

Started

2004

Primary outcome

To assess changes in fatigue in patients at least 18 years old with chronic rheumatoid arthritis (RA) and chronic anemia (Hb < 11.0 g/dL) due to ACD receiving weekly s.c. doses of PROCRIT versus placebo.

AnemiaRheumatoid Arthritis

Treatment of Anemia in Diabetic Subjects With CKD

NCT00240734Phase 2TERMINATED
Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Enrollment

11

Started

2005

Primary outcome

The primary endpoint is the hemoglobin response rate, defined as the proportion of subjects who achieve at least a 1 gram per deciliter hemoglobin increase from baseline by Week 17.

Anemia

A Phase II Study to Assess Changes in Physical Function in Elderly Patients With Chronic Anemia

NCT00228995Phase 2TERMINATED
Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Enrollment

9

Started

2004

Primary outcome

To assess the change in physical function from baseline to end of study as measured by the Short Physical Performance Battery (SPPB) summary score.

AnemiaAgedHemoglobins

Treatment for Patients With Non-Small Cell Lung Cancer Who Developed Anemia Due to Chemotherapy

NCT00120679Phase 2COMPLETED
Sponsor

Amgen

Started

2002

Primary outcome

Anemia correction

Non-Small Cell Lung CancerAnemia

Multiple Burrhole Therapy With Erythropoietin for Unstable Moyamoya

NCT03162588Phase 1/2COMPLETED
Sponsor

Ajou University School of Medicine

Enrollment

37

Started

2010

Primary outcome

Functional status of the participants after 6 months of procedure assessed by modified Rankin Scale.

Ischemic AttackIschemic StrokeMoyamoya DiseaseBurr HoleAngiogenesis

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This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer