New allosteric inhibitors of cholesterol synthesis – an alternative to statins?
Researchers in Israel have identified a new catalytic anti-oxidant that could be a promising alternative to statins – the most prescribed cholesterol-lowering drugs in the world.
Statins reduce cholesterol levels in the body by acting as competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase – the enzyme that catalyses cholesterol biosynthesis. But some patients don’t respond to statins and catalytic anti-oxidants have an advantage over statins: in their dual mode of action, they also reduce free radicals in the body.
The scientists showed that the catalytic antioxidant, Fe-1, and its analogues, inhibit HMG-CoA reductase in a different way to statins. They propose that the amphipolar nature of the drug macrocycles is important for binding to an allosteric site of HMG-coA reductase and inhibiting the enzyme’s catalytic activity.
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