Cytochrome P450 Enzymes: The Old Pandora's Box with an Ever-Growing Hope for Therapy Optimization and Drug Development-Editorial

Abstract

In 1841, the notion of drug metabolism in the body was coined with the discovery of hippuric acid as a metabolite of benzoic acid in urine of human subjects (Ure, 1841). Since then, there has been an explosive growth in our knowledge of the chemical disposition of small molecules in the human body. However, it was not until the 1960s that cytochrome P450 enzymes were identified and then recognized as the main players in small-molecule metabolism. The exponential increase in knowledge was ushered in by a progressive realization of the significance of drug metabolism and its impact on both the desired pharmacological action and the adverse effects, in addition to an incremental improvement of the accuracy and sensitivity of analytical instrumentation. Indeed, the previous five decades have witnessed a journey that started with a handful of human enzymes identified by their potential catalytic activity on certain drugs and ended with the identification of 57 genes with characteristic structural signatures following the conclusion of the human genome project.