Taken together, the articles gathered in this supplement underscore the major role in drug development that single-isomer science can play—a role that will undoubtedly take on a greater importance in the future. While the chirality of certain pharmacologically active molecules has been recognized for almost a century, it is only in recent years that drug synthesis and chiral separation techniques have advanced far enough to allow meaningful comparisons among enantiomers. Now that these methods are broadly available, the potential applications of single isomer drug development are considerable.Numerous examples from a range of therapeutic areas confirm that single enantiomers can enhance clinical efficacy, reduce adverse effects, cause fewer interactions with other drugs, and minimize response variations among patients by offering more predictable pharmacokinetics and greater selectivity. In some cases, these advantages are simply due to the removal of an inactive enantiomer, but in other cases, a given dose of a single isomer offers greater benefits when administered alone than when administered as the racemic mixture, suggesting that the opposite enantiomer (the distomer) actually has detracting effects. As the papers by Drs. Gal and Hurt explain, the different activities of a pair of enantiomers are usually traceable to stereochemical differences in the way they interact with chiral macromolecules such as enzymes, transport systems, and receptors.
The roles of computer-aided drug synthesis in drug development
