The design, development and clinical success of HIV protease inhibitors represent one of the most remarkable achievements of molecular medicine. This review describes all nine currently available FDA-approved protease inhibitors, discusses their pharmacokinetic properties, off-target activities, side-effects, and resistance profiles. The compounds in the various stages of clinical development are also introduced, as well as alternative approaches, aiming at other functional domains of HIV PR. The potential of these novel compounds to open new way to the rational drug design of human viruses is critically assessed.

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Gilead Sciences and IOCB Research Center Flemingovo n 2 166 10 Prague 6 Czech Republic; E Mails

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