Selective inhibition of mammalian lanosterol 14 alpha-demethylase by RS-21607 in vitro and in vivo.

The discovery of selective lanosterol 14α-demethylase inhibitors may lead to novel hypolipidemic drugs. RS-21607, (2S,4S)-cis-2[1H-imidazol-1-yl)methyl]-2- [2-(4-chlorophenyl)ethyl]-4- [[(4-aminophenyl)thio] methyl]-1,3-dioxolane, was characterized as a tight-binding, competitive inhibitor of lanosterol 14α-demethylase purified from rat liver. The apparent K i was determined to be 840 pM and found to be similar in hepatic microsomes from human, rat, and hamster. RS-21607, which contains two chiral centers, was a more effective lanosterol 14α-demethylase inhibitor than its three stereoisomers