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
Statin other pleiotropic cardiovascular benefits of statins, as well as in the fact that a number of other drugs that lower LDL have not shown the same cardiovascular risk benefits in studies as statins, and may also account for certain of the benefits seen in cancer reduction with statins. In addition, the inhibitory effect on protein prenylation may also be involved in a number of unwanted side effects associated with statins, including muscle pain (myopathy) and elevated blood sugar (diabetes). As noted above, statins exhibit action beyond lipid-lowering activity in the prevention of atherosclerosis. The ASTEROID trial showed direct ultrasound evidence