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
Discovery and development of statins 2 statins. One of the main differences between the type 1 and type 2 statins is the replacement of the butyryl group of type 1 statins by the fluorophenyl group of type 2 statins. This group is responsible for additional polar interactions that causes tighter binding to the HMGR enzyme. Statins that belong to this group are: Lovastatin is derived from a fungus source and simvastatin and pravastatin are chemical modifications of lovastatin and as a result do not differ much in structure from lovastatin. All three are partially reduced napthylene ring structures. Simvastatin and lovastatin are inactive lactones which