Novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase

A structure-based approach was pursued in designing novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Preliminary SAR and structural evidence for the simultaneous binding of these inhibitors into the isopentenyl pyrophosphate (IPP) and the geranyl pyrophosphate (GPP) substrate sub-pockets of the enzyme are presented.

Graphical abstractA structure-based approach was pursued in designing novel bisphosphonate active site inhibitors of the human farnesyl pyrophosphate synthase (hFPPS) that compete for binding with both IPP and risedronate.Figure optionsDownload full-size imageDownload as PowerPoint slide