Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.
Chemistry. 2020 Aug 12;26(45):10175-10184. doi: 10.1002/chem.201905792. Epub 2020 Jun 15.
The thioredoxin system is highly conserved system found in all living cells and comprises NADPH, thioredoxin, and thioredoxin reductase. This system plays a critical role in preserving a reduced intracellular environment, and its involvement in regulating a wide range of cellular functions makes it especially vital to cellular homeostasis. Its critical role is not limited to healthy cells, it is also involved in cancer development, and is overexpressed in many cancers. This makes the thioredoxin system a promising target for cancer drug development. As such, over the last decade, many inhibitors have been developed that target the thioredoxin system, most of which are small molecules targeting the thioredoxin reductase C-terminal redox center. A few inhibitors of thioredoxin have also been developed. We believe that more efforts should be invested in developing protein/peptide-based inhibitors against both thioredoxin reductase and/or thioredoxin.
硫氧还蛋白系统是一种高度保守的系统，存在于所有活细胞中，由 NADPH、硫氧还蛋白和硫氧还蛋白还原酶组成。该系统在维持还原的细胞内环境中起着关键作用，其参与调节广泛的细胞功能使其对细胞内稳态尤为重要。它的关键作用不仅限于健康细胞，它还参与癌症的发展，并在许多癌症中过度表达。这使得硫氧还蛋白系统成为癌症药物开发的有前途的靶点。因此，在过去十年中，已经开发出许多针对硫氧还蛋白系统的抑制剂，其中大多数是针对硫氧还蛋白还原酶 C 端氧化还原中心的小分子。也开发了一些针对硫氧还蛋白的抑制剂。我们认为，应该投入更多的努力来开发针对硫氧还蛋白还原酶和/或硫氧还蛋白的基于蛋白质/肽的抑制剂。
