靶向蛋白的抗肿瘤金属药物。

Matthew P Sullivan, Hannah U Holtkamp, Christian G Hartinger
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引用次数: 11

摘要

抗癌铂类药物广泛应用于多种致瘤性疾病的治疗。它们已被鉴定为靶向DNA,从而诱导癌细胞凋亡。它们对DNA以外的生物分子的反应性通常与许多癌症患者在化疗期间经历的副作用有关。针对蛋白质而不是DNA的金属化合物的开发有可能克服或至少减少常用化疗药物的缺点。许多令人兴奋的新型金属配合物具有新颖的作用模式,它们的抗癌活性与选择性蛋白质相互作用有关,这种相互作用可能导致肿瘤中积累的改善,更高的选择性和/或增强的抗增殖功效。新铅结构的开发需要生物分析方法来确认假设的作用模式或确定新的,以前未探索的生物靶点和途径。我们在本章中选择了一些原始的发展进行回顾,并重点介绍了正在走向临床应用的化合物。
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Antitumor Metallodrugs that Target Proteins.

Anticancer platinum-based drugs are widely used in the treatment of a variety of tumorigenic diseases. They have been identified to target DNA and thereby induce apoptosis in cancer cells. Their reactivity to biomolecules other than DNA has often been associated with side effects that many cancer patients experience during chemotherapy. The development of metal compounds that target proteins rather than DNA has the potential to overcome or at least reduce the disadvantages of commonly used chemotherapeutics. Many exciting new metal complexes with novel modes of action have been reported and their anticancer activity was linked to selective protein interaction that may lead to improved accumulation in the tumor, higher selectivity and/or enhanced antiproliferative efficacy. The development of new lead structures requires bioanalytical methods to confirm the hypothesized modes of action or identify new, previously unexplored biological targets and pathways. We have selected original developments for review in this chapter and highlighted compounds on track toward clinical application.

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