hERG related risk assessment of botanicals (HERGSCREEN)
hERG related risk assessment of botanicals
Date du début: 1 mars 2012,
Date de fin: 29 févr. 2016
The main goal of this project is the establishment of a network between European, South American, North American and South African educational and research entities. This attempt will be based on an innovative scientific project aiming towards the identification of hERG (human Ether-à-go-go Related Gene) channel blockers in commonly consumed botanicals and supplements. Blocking these ion channels may result in ventricular tachyarrhythmia and an increased incidence of sudden death. Thus, the hERG channel is considered as an important antitarget. Several drugs have been removed from the market for this reason, and compounds have been blocked from proceeding further into phases of clinical development. As botanicals (comprising dietary supplements, spices, herbal medicinal products) continue to increase in popularity there is an urgent need for studies aimed to critically assess the potential cardiotoxic risks of these products.State-of-the-art methodologies and techniques will be incorporated for target-oriented identification and isolation of hERG channel blocking constituents. PK and PD studies will be performed and LC-MS based methods will be developed and applied towards the measurement of bioactive components in biofluids samples. Comparison of biofluids derived from administration of single chemical entities and corresponding botanicals will be achieved using MS- and NMR-based metabolomics. The obtained results will help to elaborate and evaluate hERG related safety aspects aiming towards the risk assessment of frequently consumed botanicals.Within this frame numerous short term and extended secondments of scientific staff will be accomplished, while the organization of several workshops will assure the proper dissemination of the produced knowledge throughout all the scientific community but also the public. Core scientific knowledge is expected to be produced and exchanged, and partnerships with future scientific potentials to be created.
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