Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis
Deutscher übersetzter Titel: | HIF-Stabilisatoren und andere kleinmolekulare Erythropoese-stimulierende Mittel in der aktuellen und präventiven Dopinganalytik |
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Autor: | Beuck, Simon; Schänzer, Wilhelm; Thevis, Mario |
Erschienen in: | Drug testing and analysis |
Veröffentlicht: | 4 (2012), 11 (Sports drug testing for erythropoiesis-stimulating agents and autologous blood transfusion), S. 830-845, Lit. |
Format: | Literatur (SPOLIT) |
Publikationstyp: | Zeitschriftenartikel |
Medienart: | Gedruckte Ressource Elektronische Ressource (online) |
Sprache: | Englisch |
ISSN: | 1942-7603, 1942-7611 |
DOI: | 10.1002/dta.390 |
Schlagworte: | |
Online Zugang: | |
Erfassungsnummer: | PU201301000605 |
Quelle: | BISp |
Abstract
Increasing the blood's capacity for oxygen transport by erythropoiesis-stimulating agents (ESAs) constitutes a prohibited procedure of performance enhancement according to the World Anti-Doping Agency (WADA). The advent of orally bio-available small-molecule ESAs such as hypoxia-inducible factor (HIF) stabilizers in the development of novel anti-anaemia therapies expands the list of potential ESA doping techniques. Here, the erythropoiesis-stimulating properties and doping relevance of experimental HIF-stabilizers, such as cobaltous chloride, 3,4-dihydroxybenzoic acid or GSK360A, amongst others, are discussed. The stage of clinical trials is reviewed for the anti-anaemia drug candidates FG-2216, FG-4592, GSK1278863, AKB-6548, and BAY85-3934. Currently available methods and strategies for the determination of selected HIF stabilizers in sports drug testing are based on liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). For the support of further analytical assay development, patents claiming distinct compounds for the use in HIF-mediated therapies are evaluated and exemplary molecular structures of HIF stabilizers presented. Moreover, data concerning the erythropoiesis-enhancing effects of the GATA inhibitors K7174 and K11706 as well as the lipidic small-molecule ESA PBI-1402 are elucidated the context of doping analysis. Verf.-Referat