Discovery and development of heat shock protein 90 inhibitors.
Discovery and development of heat shock protein 90 inhibitors.
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DOI：
10.1016/j.bmc.2008.10.087
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发表时间：
2009-03-15
影响因子：
3.5
通讯作者：
Chiosis, Gabriela
中科院分区：
文献类型：
--
作者：
Taldone, Tony;Sun, Weilin;Chiosis, Gabriela
热休克蛋白90（Hsp 90）是一个重要的目标，在癌症中，因为它的作用，在维持转化，最近已成为几个药物发现和开发工作的重点。虽然具有不同的作用模式的化合物是已知的，本次审查的重点是那些类的化合物，抑制热休克蛋白90通过结合到N-末端ATP口袋。这些包括天然产物抑制剂，如格尔德霉素和根赤霉素，以及由嘌呤、吡唑、异恶唑和其他支架组成的合成抑制剂。通过基于结构的设计、高通量筛选以及最近使用基于片段的设计和虚拟筛选技术已经发现了合成抑制剂。这篇综述将讨论这些不同类别的发现，以及它们作为潜在临床药物的发展。
Heat shock protein 90 (Hsp90) is an important target in cancer because of its role in maintaining transformation and has recently become the focus of several drug discovery and development efforts. While compounds with different modes of action are known, the focus of this review is on those classes of compounds which inhibit Hsp90 by binding to the N-terminal ATP pocket. These include natural product inhibitors such as geldanamycin and radicicol and synthetic inhibitors comprised of purines, pyrazoles, isoxazoles and other scaffolds. The synthetic inhibitors have been discovered either by structure-based design, high throughput screening and more recently using fragment-based design and virtual screening techniques. This review will discuss the discovery of these different classes, as well as their development as potential clinical agents.
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影响因子：
2.7
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通讯作者：
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