Review Article

Prodrugs: design and clinical applications

  • Nature Reviews Drug Discovery volume 7, pages 255270 (2008)
  • doi:10.1038/nrd2468
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Abstract

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.

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Author information

Affiliations

  1. Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland.

    • Jarkko Rautio
    • , Hanna Kumpulainen
    •  & Tomi Järvinen
  2. Novartis Pharmaceuticals, One Health Plaza, East Hanover, New Jersey 07936-1080, USA.

    • Tycho Heimbach
  3. Gilead Sciences, 333 Lakeside Drive, Foster City, California 94404, USA.

    • Reza Oliyai
  4. Pharmacokinetics and Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA.

    • Dooman Oh
  5. Fennopharma Ltd, Microkatu 1, FI-70210, Kuopio, Finland.

    • Jouko Savolainen

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jarkko Rautio.

Glossary

Combinatorial chemistry

The rapid synthesis or the computer simulation of a large number of different but structurally related molecules.

Promoiety

A functional group used to modify the structure of pharmacologically active agents to improve physicochemical, biopharmaceutical or pharmacokinetic properties.

Co-drug

A chemical structure that undergoes conversion to two or more active drugs within a biological system, such conversion usually involves the metabolism of the co-drug.

Bioprecursor prodrug

A prodrug that does not contain a carrier or promoiety, but is metabolically or chemically transformed into an active drug.

Soft drug

Soft drugs are the opposite of prodrugs. They are active drugs that are designed to undergo a predictable and controllable deactivation or metabolism in vivo after achieving their therapeutic effect.

Bioconversion

A process in which the pharmacologically active drug is released or formed.