Using predrugs to optimize drug candidates.

INTRODUCTION: Drug discovery is a lengthy interdisciplinary approach. However, a much cheaper and less consuming predrug approach is a promising and well-established strategy for the development of new chemical entities that possess superior efficacy, selectivity and reduced toxicity. AREAS COVERED: This article provides the general terms related to predrugs, and the approaches by which predrug strategy is used to overcome many pharmaceutical and pharmacokinetic barriers. These barriers include poor bioavailability by altering the parent drug's polarity, site selectivity for enhanced absorption and less toxicity, and short duration of action to increase patient compliance. EXPERT OPINION: Utilization of the predrug approach has led to many successes and provided drugs with enhanced bioavailability and better targeting efficiency. The future of predrug strategy is a challenging and advances have to be made in understanding the chemistry of many organic reactions and the structural features of enzymes that are involved in predrug activation. The understanding of organic reaction mechanisms of certain processes will be the next major milestone in this field. It is envisioned that the future of predrug technology holds the ability to create safe and efficacious delivery of a wide range of active small molecules and biotherapeutics.