Discovery and development of statins trials showed very good inhibitory effect as in clinical trials, however in a long term toxicity study in dogs it resulted in toxic effects at higher doses and as a result was believed to be too toxic to be given to humans. In 1978, Alfred Alberts and colleagues at Merck Research Laboratories discovered a new natural product in a fermentation broth of "Aspergillus terreus", their product showed good HMGR inhibition and they named the product mevinolin, which later became known as lovastatin. The cholesterol controversy began in the early promotion of statins. Statins are a competitive antagonists of HMG CoA,
Discovery and development of statins Asp and the O5 hydroxyl group of the hydroxyglutartic acid component of the statins. Van der Waals interactions are formed between the hydrophobic side chains of the enzyme, which involve the Leu, Val, Leu, Ala and Leu and the statins. Type 2 statins form polar interaction between the fluorine atom on the fluorophenyl group and the guanidinium group of Arg. In addition to these interactions atorvastatin and rosuvastatin also form unique hydrogen bonds between Ser residue and either a carbonyl oxygen atom (atorvastatin) or a sulfone oxygen atom (rosuvastatin). A unique polar interaction between the Arg side chain and the