title: Inhibitors of human 2,3-oxidosqualene cyclase (OSC) discovered by virtual screening.
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.
authors.affiliation: Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. twatanabe@bikaken.or.jp
authors.forename: Takumi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kurata
authors.forename: Yoji
authors.initials: Y
authors.lastname: Umezawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Akamatsu
mesh_terms: D002384:Catalysis; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D007554:Isotopes / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D012307:Risk Factors; D012984:Software
chemical_list: D004791:Enzyme Inhibitors; D007554:Isotopes; D019751:Intramolecular Transferases; C021924:lanosterol synthase