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Successes, failures, and future prospects of prodrugs and their clinical impact.

INTRODUCTION: Ample efforts have been carried out to improve the efficacy of a variety of drugs. The prodrugs approach was found to be a safe haven for providing medications with improved pharmacokinetic and pharmacodynamic properties. Areas covered: Herein, several selected successful prodrugs are reported and categorized. These include prodrugs for the treatment of the cardiovascular system, the central nervous system, the gastrointestinal tract, ophthalmology, the immune system, and oncology. In addition, some successful antiviral, antibacterial, antifungal, antiprotozoal, and several other miscellaneous prodrugs are documented. Further, a number of failed prodrugs are reported followed by those potentially promising prodrugs of the future. Expert opinion: The molecular revolution and accumulation of knowledge on the chemistry of enzymes and transporters has opened the door widely to novel successful prodrugs. For example, newer platelet aggregation inhibitors could signal the end of the warfarin era with their demanding treatment follow-up. The discovery of prodrugs can significantly improve the quality of patient care. Future attention should be focused towards directed enzyme prodrug therapy (DEPT). This strategy employs the design of artificial enzymes to activate prodrugs at specific sites. Agents designed for use in DEPT medicine can be directed at antibodies, genes, viruses, and clostridia.

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