Discovery and development of heat shock protein 90 inhibitors Journal Article
| Authors: | Taldone, T.; Sun, W.; Chiosis, G. |
| Article Title: | Discovery and development of heat shock protein 90 inhibitors |
| Abstract: | 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. © 2008 Elsevier Ltd. All rights reserved. |
| Keywords: | unclassified drug; clinical trial; nonhuman; protein function; neoplasm; animals; unindexed drug; multiple myeloma; breast cancer; high throughput screening; drug screening; drug discovery; drug design; structure activity relation; pyrazole derivative; pyrazoles; 17 demethoxy 17 (2 dimethylaminoethylamino)geldanamycin; heat shock protein 90 inhibitor; tanespimycin; heat shock protein 90; hsp90 heat-shock proteins; purines; binding sites; purine derivative; adenosine triphosphate; natural product; drug protein binding; tanespimycin hydroquinone; geldanamycin; isoxazoles; pu-class; radicicol; 2 cyclopropylaminoethyl derivative; 3 (5 chloro 2,4 dihydroxyphenyl) n ethyl 4 (4 methoxyphenyl) 5 pyrazolecarboxamide; 4 [4 (1,4 benzodioxan 6 yl) 5 methyl 1h pyrazol 3 yl] 6 ethylresorcinol; cct 072440; cct 08159; cycloproparadicicol; g 3129; isoxazole derivative; kf 25706; kos 1022; kosn 1559; nvp auy 922; oxime derivative; pochonin a; pochonin d; pyridothiophene derivative; pyridylmethyl derivative; pyrimidothiophene derivative; radamide; radester; ver 50589 |
| Journal Title: | Bioorganic & Medicinal Chemistry |
| Volume: | 17 |
| Issue: | 6 |
| ISSN: | 0968-0896 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2009-03-15 |
| Start Page: | 2225 |
| End Page: | 2235 |
| Language: | English |
| DOI: | 10.1016/j.bmc.2008.10.087 |
| PUBMED: | 19017562 |
| PROVIDER: | scopus |
| PMCID: | PMC2760286 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 37" - "Export Date: 30 November 2010" - "CODEN: BMECE" - "Source: Scopus" |
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