Ludwig-Maximilians University Munich, Department of Obstetrics/Gynecology, Campus Innenstadt, Munich, Germany.
Curr Mol Pharmacol. 2010 Jun;3(2):91-7. doi: 10.2174/1874467211003020091.
Nelfinavir (Viracept) was originally designed as a specific HIV protease inhibitor and, since its introduction in 1997, has served as an effective, reliable, and well-tolerated HIV drug. Although nelfinavir is being increasingly displaced by second generation HIV protease inhibitors that allow better combination treatments, it has again become a focus of interest due to an interesting paradoxical effect: nelfinavir inhibits experimentally-induced tissue degeneration or cell damage by preventing loss of the mitochondrial membrane potential, and even protects mitochondria in cancer cells but, conversely, it selectively induces a mitochondria-independent cell death mechanism in cancer cells by the so-called endoplasmic reticulum/unfolded protein stress response, allowing nelfinavir to act on otherwise chemo-resistant cancer cells. Furthermore, anti-microbial effects of nelfinavir have been described, including an efficacy against malaria, tuberculosis, and SARS. Several cancer-related clinical studies on nelfinavir as a single agent or in combination therapies have been launched and are expected to add to the usefulness of this versatile drug for cancer treatment strategies or other purposes.
奈非那韦（Viracept）最初被设计为一种特定的 HIV 蛋白酶抑制剂，自 1997 年推出以来，它一直是一种有效、可靠且耐受性良好的 HIV 药物。尽管奈非那韦正逐渐被允许更好地联合治疗的第二代 HIV 蛋白酶抑制剂所取代，但由于一个有趣的矛盾效应，它再次成为关注的焦点：奈非那韦通过防止线粒体膜电位丧失来抑制实验诱导的组织退化或细胞损伤，甚至保护癌细胞中的线粒体，但相反，它通过所谓的内质网/未折叠蛋白应激反应选择性地诱导一种线粒体非依赖性的癌细胞死亡机制，使奈非那韦能够作用于原本对化疗耐药的癌细胞。此外，奈非那韦还具有抗微生物作用，包括对疟疾、结核病和 SARS 的疗效。已经启动了几项关于奈非那韦作为单一药物或联合治疗的癌症相关临床研究，预计将增加这种多功能药物在癌症治疗策略或其他用途方面的效用。
