Microbial Metabolites and Enzymes Inhibition in Drug Discovery and Development: A Case Study of the Statins, a Class of HMG-CoA Reductase Inhibitors. Trop J Nat Prod Res
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Tropical Journal of Natural Product Research
The discovery and development of the statins provides an insight into the many facets of the drug discovery process and also shows the time and resources that must be devoted to developing a clinically useful drug from an initial concept. It began from the conceptual search for metabolites that could inhibit an important enzyme in cholesterol biosynthesis, HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, to the isolation of the first active metabolite, citrinin, from a fungus, leading to further search and development. This discovery is a milestone in medicine and a historical portrait, which illustrates the importance of multidisciplinary approach in drug development. The statins are the results of combined efforts of inter alia, pharmaceutical chemists, microbiologists, physiologists, and pharmacologists. This paper gives an account of the discovery of the statins, highlighting the clinical importance of cholesterol, the discovery of HMG-CoA reductase, and subsequent search for its inhibitors. It showcases the clinical importance and limitations of the statins and seeks to serve as a guide and inspiration for future discovery and development of novel, potent and safer cholesterol-lowering agents.
Drug discovery , Microbial metabolites , HMG-CoA reductase inhibitors , Cholesterol-lowering agents , Akira Endo , Research Subject Categories::PHARMACY