Zaragozic Acid A

Squalene synthase catalyzes the first committed step in cholesterol synthesis, mediating the reductive dimerization of farnesyl pyrophosphate (Item No. 63250) to produce squalene.{15286} Zaragozic acid A is a fungal metabolite that acts as a reversible competitive inhibitor of squalene synthase (Ki = 78 pM in vitro).{28249} It dose-dependently reduces cholesterol synthesis in HepG2 cells (IC50 = 6 µM) and inhibits hepatic cholesterol synthesis in mice (ED50 = 0.2 mg/kg).{28249} Zaragozic acid A also inhibits farnesyl transferase (FTase) and geranylgeranyl transferase type I (GGTase I) (IC50s = 216 and 50 nM, respectively).{1196}