Going to bis-school
A team at Novartis AG has identified the first non-bisphosphonate inhibitors of farnesyl diphosphate synthase,1 an enzyme targeted by bone-specific bisphosphonates that are approved to treat benign and malignant bone diseases. The researchers believe the lower bone affinities of the new class of inhibitors could make the molecules better suited than bisphosphonates for cancer indications including soft tissue tumors.
However, safety could be a concern with these new compounds, as the target is part of the central mevalonate metabolic pathwaythat affects both cholesterol synthesis and protein prenylation2 (see "Targeting the mevalonate pathway").
In bone diseases, bisphosphonates decrease prenylation of