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Review

Nature Reviews Drug Discovery 7, 255–270 (1 February 2008) | doi:10.1038/nrd2468

Prodrugs: design and clinical applications

Jarkko Rautio , Hanna Kumpulainen , Tycho Heimbach , Reza Oliyai , Dooman Oh , Tomi J|[auml]|rvinen & Jouko Savolainen

Prodrugs are bioreversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then exert the desired pharmacological effect. In both drug discovery and development, prodrugs have become an established tool for improving physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically active agents. About 5–7% of drugs approved worldwide can be classified as prodrugs, and the implementation of a prodrug approach in the early stages of drug discovery is a growing trend. To illustrate the applicability of the prodrug strategy, this article describes the most common functional groups that are amenable to prodrug design, and highlights examples of prodrugs that are either launched or are undergoing human trials.