Discovery and development of statins as they directly compete with the endogenous substrate for the active site cavity of HMGR. Statins are also noncompetitive with the cosubstrate NADPH (nicotinamide adenine dinucleotide phosphate). By blocking the HMGR enzyme they inhibit the synthesis of cholesterol via the mevalonate pathway. The end result is lower LDL (Low Density Lipoprotein), TG (Triglycerides) and total cholesterol levels as well as increased HDL (High Density Lipoprotein) levels in serum). The ideal statin should have the following properties: One of the main design objectives of statin design is the selective inhibition of HMGR in the liver, as cholesterol synthesis in non-hepatic cells
Chronic endothelial injury hypothesis the hypertension often seen with atherosclerosis. The role LDL plays suggests two different approaches to treatment and prevention. The first approach involves discouraging the accumulation of LDL by lowering the levels of serum LDL, an idea more closely associated with the lipid hypothesis. A major breakthrough involved the discovery of statins, a class of drugs which help to clear LDL from the bloodstream. It has been demonstrated conclusively that elevated levels of LDL are associated with higher risk of mortality from coronary heart disease (CHD); it has also been shown that statins substantially lower the risk of mortality in patients