Erythropoiesis stimulating agents and techniques : a challenge for doping analysts

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Bibliographic Details
Title translated into German:Stimulanz-Wirkstoffe und Techniken der Erythropoese : Anknüpfungspunkte für Dopinganalytiker
Author:Jelkmann, Wolfgang
Published in:Current medicinal chemistrychemistry
Published:16 (2009), 10, S. 1236-1247, Lit.
Format: Publications (Database SPOLIT)
Publication Type: Journal article
Media type: Print resource
Language:English
ISSN:0929-8673, 1875-533X
Keywords:
Online Access:
Identification number:PU201007005529
Source:BISp

Author's abstract

Recombinant human erythropoietin (rHuEPO) engineered in Chinese hamster ovary (CHO) cell cultures (Epoetin alfa and Epoetin beta) and its hyperglycosylated analogue Darbepoetin alfa are known to be misused by athletes. The drugs can be detected by isoelectric focusing (IEF) and immunoblotting of urine samples, because “EPO” is in reality a mixture of isoforms and the N-glycans of the recombinant products differ from those of the endogenous hormone. However, there is a plethora of novel erythropoiesis stimulating agents (ESAs). Since the originator Epoetins alfa and beta are no longer protected by patent in the European Union, rHuEPO biosimilars have entered the market. In addition, several companies in Asia, Africa and Latin America produce copied rHuEPOs for clinical purposes. While the amino acid sequence of all Epoetins is identical, the structure of their glycans differs depending on the mode of production. Some products contain more acidic and others more basic EPO isoforms. Epoetin delta is special, as it was engineered by homologous recombination in human fibrosarcoma cells (HT-1080), thus lacking N-glycolylneuraminic acid like native human EPO. ESAs under development include EPO fusion proteins, synthetic erythropoiesis stimulating protein (SEP) and peptidic (HematideTM, CNTO 528) as well as non-peptidic EPO mimetics. Furthermore, preclinical respectively clinical trials have been performed with small orally active drugs that stimulate endogenous EPO production by activating the EPO promoter (“GATA-inhibitors”: diazepane derivatives) or enhancer (“HIF-stabilizers”: 2-oxoglutarate analogues). The prohibited direct EPO gene transfer may become a problem in sports only in the future. Verf.-Referat