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:
Viruses. 2009 Dec;1(3):1209-39. doi: 10.3390/v1031209. Epub 2009 Dec 11.
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.
HIV 蛋白酶抑制剂的设计、开发和临床成功代表了分子医学最显著的成就之一。本文综述了目前所有 9 种获得美国 FDA 批准的蛋白酶抑制剂，讨论了它们的药代动力学特性、非靶标活性、副作用和耐药谱。还介绍了处于不同临床开发阶段的化合物，以及针对 HIV PR 其他功能域的其他方法。本文还批判性地评估了这些新型化合物在合理设计针对人类病毒的药物方面的潜力。
