Toogood Peter L
Lycera Corporation, 1663 Snowberry Ridge Road, Ann Arbor, MI 48103, USA.
Curr Opin Chem Biol. 2008 Aug;12(4):457-63. doi: 10.1016/j.cbpa.2008.06.002. Epub 2008 Jul 2.
Mitochondria are cellular organelles that perform pivotal functions essential for ATP production, homeostasis, and metabolism. Moreover, mitochondria are integral to a variety of cell death and survival pathways. These roles identify mitochondria as a potential target for drugs to treat metabolic and hyperproliferative diseases. Differences in the redox state of pathogenic versus non-pathogenic cells may be exploited to achieve selective anti-proliferative and cytotoxic activity against target cell populations. Pro-oxidant drugs, such as Trisenox and Elesclomol, are demonstrating clinical utility in the treatment of cancer. Results obtained with Bz-423 in mice demonstrate the potential for mitochondria-targeted drugs to control disorders of immune function. Research associating an elevated oxidant state with mitochondrial damage, degenerative disease, and aging dictates the need for a better understanding of when and how pharmacological manipulation of mitochondrial function provides most therapeutic benefit.
线粒体是细胞细胞器，执行对ATP产生、体内平衡和新陈代谢至关重要的关键功能。此外，线粒体是多种细胞死亡和存活途径所不可或缺的。这些作用表明线粒体是治疗代谢性疾病和过度增殖性疾病药物的潜在靶点。可利用致病细胞与非致病细胞氧化还原状态的差异，来实现对靶细胞群体的选择性抗增殖和细胞毒性活性。促氧化剂药物，如三氧化二砷和依列莫司，在癌症治疗中显示出临床应用价值。用Bz - 423在小鼠身上获得的结果表明，线粒体靶向药物有控制免疫功能紊乱的潜力。将氧化状态升高与线粒体损伤、退行性疾病和衰老联系起来的研究表明，需要更好地了解何时以及如何通过药理学手段操纵线粒体功能能带来最大的治疗益处。
