alexa Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors.


Journal of Microbial & Biochemical Technology

Author(s): Tobert JA

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Abstract In the 1950s and 1960s, it became apparent that elevated concentrations of plasma cholesterol were a major risk factor for the development of coronary heart disease, which led to the search for drugs that could reduce plasma cholesterol. One possibility was to reduce cholesterol biosynthesis, and the rate-limiting enzyme in the cholesterol biosynthetic pathway, 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, was a natural target. Here, I describe the discovery and development of lovastatin--the first approved inhibitor of HMG-CoA reductase--and the clinical trials that have provided the evidence for the ability of drugs in this class to reduce the morbidity and mortality associated with cardiovascular disease. This article was published in Nat Rev Drug Discov and referenced in Journal of Microbial & Biochemical Technology

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