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探索基于金属的候选药物作为细胞骨架调节剂的潜力。

Exploring the Potential of Metal-Based Candidate Drugs as Modulators of the Cytoskeleton.

机构信息

Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, 1090, Vienna, Austria.

Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, 1090, Vienna, Austria.

出版信息

Chembiochem. 2023 Sep 1;24(17):e202300178. doi: 10.1002/cbic.202300178. Epub 2023 Aug 1.

Abstract

During recent years, accumulating evidence suggested that metal-based candidate drugs are promising modulators of cytoskeletal and cytoskeleton-associated proteins. This was substantiated by the identification and validation of actin, vimentin and plectin as targets of distinct ruthenium(II)- and platinum(II)-based modulators. Despite this, structural information about molecular interaction is scarcely available. Here, we compile the scattered reports about metal-based candidate molecules that influence the cytoskeleton, its associated proteins and explore their potential to interfere in cancer-related processes, including proliferation, invasion and the epithelial-to-mesenchymal transition. Advances in this field depend crucially on determining binding sites and on gaining comprehensive insight into molecular drug-target interactions. These are key steps towards establishing yet elusive structure-activity relationships.

摘要

近年来,越来越多的证据表明,基于金属的候选药物是细胞骨架和细胞骨架相关蛋白的有前途的调节剂。这一点得到了明确和验证,即肌动蛋白、波形蛋白和网蛋白是不同的钌(II)和铂(II)基调节剂的靶点。尽管如此,关于分子相互作用的结构信息却很少。在这里,我们汇集了关于影响细胞骨架及其相关蛋白的基于金属的候选分子的分散报告,并探讨了它们在包括增殖、侵袭和上皮间质转化在内的与癌症相关的过程中发挥作用的潜力。该领域的进展在很大程度上取决于确定结合位点并全面了解分子药物-靶标相互作用。这些是建立至今仍难以捉摸的构效关系的关键步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/848a/10946712/9ee3c97017c9/CBIC-24-0-g004.jpg

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