The ProTide Prodrug Technology: From the Concept to the Clinic

Youcef Mehellou, Hardeep Rattan

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77 Citations (Scopus)
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The ProTide technology is a prodrug approach developed for the efficient intracellular delivery of nucleoside analogue monophosphates and monophosphonates. In this approach, the hydroxyls of the monophosphate or monophosphonate groups are masked by an aromatic group and an amino acid ester moiety, which are enzymatically cleaved-off inside cells to release the free nucleoside monophosphate and monophosphonate species. Structurally, this represents the current end-point of an extensive medicinal chemistry endeavour that spans almost three decades. It started from the masking of nucleoside monophosphate and monophosphonate groups by simple alkyl groups and evolved into the sophisticated ProTide system as known today. This technology has been extensively employed in drug discovery and it has already led to the discovery of two FDA-approved (antiviral) ProTides. In this work, we will review the development of the ProTide technology, its application in drug discovery and its role in the improvement of drug delivery and efficacy.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Early online date9 Aug 2017
Publication statusE-pub ahead of print - 9 Aug 2017


  • Nucleoside
  • Cancer
  • ProTide
  • Prodrug
  • Antiviral


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