Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases.
Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases.
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DOI：
10.1017/s1462399411002031
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发表时间：
2011-11-17
影响因子：
6.2
通讯作者：
Kessler BM
中科院分区：
文献类型：
--
作者：
Edelmann MJ;Nicholson B;Kessler BM
药物干预的开发和发现的最新进展 泛素-蛋白酶体系统（UPS）已经揭示了 神经退行性疾病、癌症、免疫紊乱和 微生物感染干扰蛋白酶体活性，尽管最初认为 不太可能在临床上利用，已经证明对 血液学恶性肿瘤，以及靶向以下亚群的更特异性衍生物： 蛋白酶体正在出现。最近的小分子筛选显示， 泛素结合和去结合酶，其中许多已被评估为 它们作为治疗剂的潜在用途，或者作为单一药剂或者与其它药剂协同， 毒品在这里，我们讨论了新的UPS调制器的特性的最新进展 (in特别是，泛素结合和去结合酶的抑制剂）以及如何 它们为治疗蛋白毒性的新治疗方法铺平了道路。 疾病、癌症和微生物感染。
Recent advances in the development and discovery of pharmacological interventions within the ubiquitin–proteasome system (UPS) have uncovered an enormous potential for possible novel treatments of neurodegenerative disease, cancer, immunological disorder and microbial infection. Interference with proteasome activity, although initially considered unlikely to be exploitable clinically, has already proved to be very effective against haematological malignancies, and more specific derivatives that target subsets of proteasomes are emerging. Recent small-molecule screens have revealed inhibitors against ubiquitin-conjugating and -deconjugating enzymes, many of which have been evaluated for their potential use as therapeutics, either as single agents or in synergy with other drugs. Here, we discuss recent advances in the characterisation of novel UPS modulators (in particular, inhibitors of ubiquitin-conjugating and -deconjugating enzymes) and how they pave the way towards new therapeutic approaches for the treatment of proteotoxic disease, cancer and microbial infection.