β-L-Hydroxycytosin – a novel class of Nucleoside Analogue Reverse Transcriptase Inhibitors for the Treatment of Hepatitis B Viral Infections
Today more than 350 million people are infected with the Hepatitis B virus (HBV) throughout the world. Despite established vaccine strategies, the global challenge of the chronic disease is still alive, in particular considering quick development of resistance strains and novel effective HBV drugs are still required.
b-L-Hydroxycytosin nucleotide derivatives are a novel compound class of nucleoside analogue reverse transcriptase inhibitors (NRTI) for the treatment of HBV infection with extremely low cytotoxicity compared to known HBV drugs. In cellular assays, the compounds show up to three-fold lower IC50 values than the HBV drug Lamivudin. Cellular, including mitochondrial, polymerases, are significantly less sensitive to the compounds (>>70µM), demonstrating HBV Polymerase selectivity. Only a very low mutagenity was detectable in a mini-AMES assay. First in vivo experiments also indicate no cytotoxic side effect of the substances, making them promising candidates for the development of anti-HBV drugs and broadening the compound portfolio for HBV combination therapy.
Exclusive in-licensing opportunity for the development of a HBV drug.
Pre-clinical in vitro proof of concept in biochemical and cellular assays. Initial confidential in vivo results available.
Patent applications based on WO 2006/045616 are pending in Europe and USA.