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Comprehensive in vitro pharmacological selectivity profile of oseltamivir prodrug (Tamiflu®) and oseltamivir active metabolite
Author(s) -
Lindemann Lothar,
Jacobsen Helmut,
Schweitzer Christophe,
Schuhbauer Diana,
Reinhardt Dieter,
Fischer Christophe,
Diener Catherine,
McArthur Silvia Gatti,
Beck Jennifer,
Wettstein Joseph G.,
Loetscher Hansruedi,
Prinssen Eric,
Brockhaus Manfred
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.671
Subject(s) - oseltamivir , neuraminidase , prodrug , neuraminidase inhibitor , metabolite , virus , pharmacology , active metabolite , influenza a virus , chemistry , in vitro , enzyme , virology , drug , ic50 , orthomyxoviridae , biology , biochemistry , medicine , disease , covid-19 , infectious disease (medical specialty)
Oseltamivir is a potent and selective inhibitor of the influenza virus neuraminidases, specifically targeting influenza virus A‐ and B‐subtypes including the A/H5N1 influenza virus. To date, the drug has been administered to almost 50 million subjects for the treatment or prophylaxis of influenza. Here we present a comprehensive in vitro pharmacological profile of oseltamivir prodrug (OP) and oseltamivir active metabolite (OC). The assessment of both compounds in a panel of 155 radio‐ligand binding and functional in vitro assays covering a broad range of receptors, enzymes and ion channels, including CNS‐related targets, confirmed the lack of any relevant off‐target activity of OP and OC. Enzymatic studies employing recombinant influenza neuraminidase and all four known human neuraminidases revealed an IC 50 ~ 1 nM of OC on influenza neuraminidase and no detectable inhibitory activity of OP and OC on any of the four human neuraminidases at concentrations up to 1 mM. Our pharmacological data revealed selective activity only against the influenza virus neuraminidase in line with previous reports and further consolidate the selectivity of the drug.