Center for Discovery and Innovation in Diseases (CDIPD), Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA, United States; Department of Chemistry and Biochemistry, University of California, San Diego, CA, United States.
Center for Discovery and Innovation in Diseases (CDIPD), Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA, United States.
Adv Parasitol. 2024;126:53-96. doi: 10.1016/bs.apar.2024.04.001. Epub 2024 Sep 23.
The proteasome is a proteolytically active molecular machine comprising many different protein subunits. It is essential for growth and survival in eukaryotic cells and has long been considered a drug target. Here, we summarize the biology of the proteasome, the early research relating to the development of specific proteasome inhibitors (PIs) for treatment of various cancers, and their translation and eventual evolution as exciting therapies for parasitic diseases. We also highlight the development and adaptation of technologies that have allowed for a deep understanding of the idiosyncrasies of individual parasite proteasomes, as well as the preclinical and clinical advancement of PIs with remarkable therapeutic indices.
蛋白酶体是一种具有蛋白水解活性的分子机器，由许多不同的蛋白质亚基组成。它对真核细胞的生长和存活至关重要，长期以来一直被视为药物靶点。在这里，我们总结了蛋白酶体的生物学特性、早期与开发用于治疗各种癌症的特定蛋白酶体抑制剂 (PI) 相关的研究，以及它们作为寄生虫病治疗方法的转化和最终发展。我们还强调了技术的发展和适应性，这些技术使我们能够深入了解寄生虫蛋白酶体的特殊性，以及具有显著治疗指数的 PI 的临床前和临床进展。
