Inhibitors of human 2,3-oxidosqualene cyclase (OSC) discovered by virtual screening
Takumi Watanabe1, Ikuko Kurata, Yoji Umezawa
1Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. twatanabe@bikaken.or.jp
Abstract:
Five human 2,3-oxidosqualnene cyclase (OSC) inhibitors were discovered using the combination of a virtual screening based on a docking study and an isotope-free assay system. All of these inhibitors were revealed to have activities comparable or superior to that of LDAO, a known OSC inhibitor. The computational study of the newly identified inhibitors suggested that CH/π interactions with F444 and W581 contribute to the binding, and these interactions are candidates for additional structural filters in the next generation of virtual screening.
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