Targeting wide-range oncogenic transformation via PU24FCI, a specific inhibitor of tumor Hsp90 Journal Article
| Authors: | Vilenchik, M.; Solit, D.; Basso, A.; Huezo, H.; Lucas, B.; He, H.; Rosen, N.; Spampinato, C.; Modrich, P.; Chiosis, G. |
| Article Title: | Targeting wide-range oncogenic transformation via PU24FCI, a specific inhibitor of tumor Hsp90 |
| Abstract: | Agents that inhibit Hsp90 function hold significant promise in cancer therapy. Here we present PU24FCl, a representative of the first class of designed Hsp90 inhibitors. By specifically and potently inhibiting tumor Hsp90, PU24FCl exhibits wide-ranging anti-cancer activities that occur at similar doses in all tested tumor types. Normal cells are 10- to 50-fold more resistant to these effects. Its Hsp90 inhibition results in multiple anti-tumor-specific effects, such as degradation of Hsp90-client proteins involved in cell growth, survival, and specific transformation, inhibition of cancer cell growth, delay of cell cycle progression, induction of morphological and functional changes, and apoptosis. In concordance with its higher affinity for tumor Hsp90, in vivo PU24FCl accumulates in tumors while being rapidly cleared from normal tissue. Concentrations achieved in vivo in tumors lead to single-agent anti-tumor activity at non-toxic doses. |
| Keywords: | antineoplastic agents; antineoplastic agent; neoplasm; neoplasms; mouse; animal; animals; mice; cell survival; cell division; cell line; drug effect; drug screening; drug screening assays, antitumor; cell line, tumor; drug design; time; time factors; cell transformation, neoplastic; chemistry; drug antagonism; nude mouse; mice, nude; cell transformation; tumor cell line; drug derivative; heat shock protein 90; hsp90 heat-shock proteins; chemical structure; molecular structure; adenine; anisoles; humans; human; female; article; 2 fluoro 8 ((2 chloro 3,4,5, trimethoxyphenyl)methyl) 9 pentyladenine; 2-fluoro-8-((2-chloro-3,4,5,-trimethoxyphenyl)methyl)-9-pentyladenine; anisole derivative |
| Journal Title: | Chemistry and Biology |
| Volume: | 11 |
| Issue: | 6 |
| ISSN: | 1074-5521 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2004-06-01 |
| Start Page: | 787 |
| End Page: | 797 |
| Language: | English |
| DOI: | 10.1016/j.chembiol.2004.04.008 |
| PROVIDER: | scopus |
| PUBMED: | 15217612 |
| DOI/URL: | |
| Notes: | Chem. Biol. -- Cited By (since 1996):124 -- Export Date: 16 June 2014 -- CODEN: CBOLE -- Source: Scopus |
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