Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0596, USA.
Cell Biochem Biophys. 2013 Sep;67(1):91-101. doi: 10.1007/s12013-013-9626-4.
Over the years, the proteasome has been extensively investigated due to its crucial roles in many important signaling pathways and its implications in diseases. Two proteasome inhibitors--bortezomib and carfilzomib--have received FDA approval for the treatment of multiple myeloma, thereby validating the proteasome as a chemotherapeutic target. As a result, further research efforts have been focused on dissecting the complex biology of the proteasome to gain the insight required for developing next-generation proteasome inhibitors. It is clear that chemical probes have made significant contributions to these efforts, mostly by functioning as inhibitors that selectively block the catalytic activity of proteasomes. Analogues of these inhibitors are now providing additional tools for visualization of catalytically active proteasome subunits, several of which allow real-time monitoring of proteasome activity in living cells as well as in in vivo settings. These imaging probes will provide powerful tools for assessing the efficacy of proteasome inhibitors in clinical settings. In this review, we will focus on the recent efforts towards developing imaging probes of proteasomes, including the latest developments in immunoproteasome-selective imaging probes.
多年来，蛋白酶体因其在许多重要信号通路中的关键作用及其在疾病中的意义而受到广泛研究。两种蛋白酶体抑制剂——硼替佐米和卡非佐米——已获得 FDA 批准用于治疗多发性骨髓瘤，从而验证了蛋白酶体作为化疗靶点的合理性。因此，进一步的研究重点集中在剖析蛋白酶体的复杂生物学，以获得开发下一代蛋白酶体抑制剂所需的深入了解。很明显，化学探针在这些努力中做出了重大贡献，主要是作为抑制剂，选择性地阻断蛋白酶体的催化活性。这些抑制剂的类似物现在为催化活性蛋白酶体亚基的可视化提供了额外的工具，其中一些允许实时监测活细胞以及体内环境中的蛋白酶体活性。这些成像探针将为评估蛋白酶体抑制剂在临床环境中的疗效提供有力工具。在这篇综述中，我们将重点介绍开发蛋白酶体成像探针的最新进展，包括免疫蛋白酶体选择性成像探针的最新进展。
