Tsukamoto Sachiko, Yokosawa Hideyoshi
Chiba University, Graduate School of Science, 1-33 Yayoi-cho, Inage-ku, Chiba 263 8522, Japan.
Expert Opin Ther Targets. 2009 May;13(5):605-21. doi: 10.1517/14728220902866851.
The ubiquitin-proteasome pathway functions as a main pathway in intracellular protein degradation and plays a vital role in almost all cellular events. Various inhibitors of this pathway have been developed for research purposes. The recent approval of bortezomib (PS-341, Velcade, a proteasome inhibitor, for the treatment of multiple myeloma has opened the way to the discovery of drugs targeting the proteasome and other components of the ubiquitin-proteasome pathway.
We review the current understanding of the ubiquitin-proteasome pathway and inhibitors targeting this pathway, including proteasome inhibitors, as candidate drugs for chemical therapy.
Preclinical and clinical data for inhibitors of the proteasome and the ubiquitin-proteasome pathway are discussed.
The proteasome and other members in the ubiquitin-proteasome pathway have emerged as novel therapeutic targets.
泛素-蛋白酶体途径是细胞内蛋白质降解的主要途径，在几乎所有细胞活动中都起着至关重要的作用。为了研究目的，已经开发了该途径的各种抑制剂。硼替佐米（PS-341，万珂，一种蛋白酶体抑制剂）最近被批准用于治疗多发性骨髓瘤，这为发现靶向蛋白酶体和泛素-蛋白酶体途径其他成分的药物开辟了道路。
我们综述了目前对泛素-蛋白酶体途径以及靶向该途径的抑制剂（包括蛋白酶体抑制剂）作为化学治疗候选药物的认识。
讨论了蛋白酶体和泛素-蛋白酶体途径抑制剂的临床前和临床数据。
蛋白酶体和泛素-蛋白酶体途径中的其他成员已成为新的治疗靶点。
