Development of a purine-scaffold novel class of hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase Journal Article
| Authors: | Chiosis, G.; Lucas, B.; Shtil, A.; Huezo, H.; Rosen, N. |
| Article Title: | Development of a purine-scaffold novel class of hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase |
| Abstract: | The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71) exhibits binding to hsp90 comparable to the natural product derivative 17AAG that is now in Phase I clinical trial as a cancer therapeutic. 71 Induces the degradation of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low micromolar concentrations (IC50=2 μM). © 2002 Elsevier Science Ltd. All rights reserved. |
| Keywords: | cancer chemotherapy; controlled study; unclassified drug; human cell; drug activity; antineoplastic agents; cell proliferation; cell division; breast cancer; enzyme degradation; protein binding; cancer cell culture; drug screening assays, antitumor; tumor cells, cultured; protein tyrosine kinase; drug synthesis; structure-activity relationship; cancer cell; magnetic resonance spectroscopy; heat shock protein 90; hsp90 heat-shock proteins; purines; receptor, erbb-2; purine derivative; alkylation; ic 50; drug binding; concentration response; protein inhibitor; peptide library; indicators and reagents; geldanamycin; oncogene neu; spectrophotometry, ultraviolet; humans; human; article; mink cell focus-forming virus; 2 fluoro 9 pent 4 ynyl 8 (2 chloro 3,4,5 trimethoxybenzyl) 9h purin 6 ylamine |
| Journal Title: | Bioorganic & Medicinal Chemistry |
| Volume: | 10 |
| Issue: | 11 |
| ISSN: | 0968-0896 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2002-11-01 |
| Start Page: | 3555 |
| End Page: | 3564 |
| Language: | English |
| DOI: | 10.1016/s0968-0896(02)00253-5 |
| PUBMED: | 12213470 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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