Prevalence of Scaffolds in Human Cytochrome P450 Inhibitors Identified Using the LOPAC1280 Library of Pharmacologically Active Compounds

Introduction The cytochromes P450 (CYP) are oxidative enzymes involved in multiple biochemical pathways, including drug metabolism and clearance of toxicants from the body [1]. Certain drugs or chemicals can inhibit CYP enzyme function, which alters their ability to metabolize drugs. The resulting toxic effects are referred to as drug-drug interactions and are a major concern for drug development. Therefore, CYP inhibition is being considered more thoroughly at earlier stages in drug discovery [2]. Computational methods to study and predict CYP inhibition have garnered significant interest, and methods like pharmacophore analysis and multivariate statistical modeling are widely used [3-5]. As an alternative approach, we present a chemical subgraph method to describe the scaffolds prevalent in compounds that inhibit CYP enzymes. The goal is to organize knowledge about CYP inhibition around chemical substructures, so that simple guidelines can be provided to researchers in their daily efforts to design better drug-like molecules.