Lovastatin and simvastatin

Once the rate-limiting role of HMG-CoA reductase in cholesterol biosynthesis was understood, specific inhibitors were sought to lower blood cholesterol levels.

The compounds discovered are collectively called statins.

They act by competitively inhibiting HMG-CoA reductase.

Lovastatin and simvastatin are fungal polyketides and atorvastatin (Lipitor®) is synthetic.

Each statin carries a mevalonate-like moiety (blue), explaining the competitive nature of their activity.

Inhibition of HMG-CoA reductase depresses de novo cholesterol biosynthesis and, hence, intracellular cholesterol levels.

This in turn leads to increased production of LDL receptors, allowing more rapid clearance of extracellular cholesterol from the blood, thus lowering blood cholesterol levels.