Weekley Claire M, He Chuan
Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
Curr Opin Chem Biol. 2017 Apr;37:26-32. doi: 10.1016/j.cbpa.2016.12.011. Epub 2016 Dec 29.
Metal dyshomeostasis is involved in the pathogenesis and progression of diseases including cancer and neurodegenerative diseases. Metal chelators and ionophores are well known modulators of transition metal homeostasis, and a number of these molecules are in clinical trials. Metal-binding compounds are not the only drugs capable of targeting transition metal homeostasis. This review presents recent highlights in the development of chelators and ionophores for the treatment of cancer and neurodegenerative disease. Moreover, we discuss the development of small molecules that alter copper and iron homeostasis by inhibiting metal transport proteins. Finally, we consider the emergence of metal regulatory factor 1 as a drug target in diseases where it mediates zinc-induced signalling cascades leading to pathogenesis.
金属稳态失衡参与包括癌症和神经退行性疾病在内的多种疾病的发病机制和进展过程。金属螯合剂和离子载体是众所周知的过渡金属稳态调节剂，其中一些分子正处于临床试验阶段。金属结合化合物并非唯一能够靶向过渡金属稳态的药物。本综述介绍了用于治疗癌症和神经退行性疾病的螯合剂和离子载体开发方面的最新亮点。此外，我们还讨论了通过抑制金属转运蛋白来改变铜和铁稳态的小分子的开发情况。最后，我们考虑了金属调节因子1作为药物靶点在疾病中的出现，在这些疾病中它介导锌诱导的信号级联反应并导致发病机制。
