Figure 1.

Non-macrolide FKBP-inihibitors. Shown are the two main building blocks of the novel FKBP inhibitors presented in this study. (A) Cycloheximide N-ethylethanoate is a non-toxic derivative of the natural compound cycloheximide, an inhibitor of eukaryotic translation. (B) Adamantane was identified by structure based computational modeling as an appropriate scaffold that can replace the pipecolinic acid moiety in FK506, which interacts with the PPIase active cleft of FKBPs. Adamantane and substituents of it were fused to N-(carboxymethyl)cycloheximide in order to produce novel cycloheximide derivatives (see also Table 1).