Novel Nitrogen Mustard-Armed Combi-Molecules for the Selective Targeting of Epidermal Growth Factor Receptor Overexperessing Solid Tumors: Discovery of an Unusual Structure−Activity Relationship
| Autor: | Janet M. Hartley, Qiyu Qiu, John A Hartley, Bertrand J. Jean-Claude, Christopher Williams, Fouad Brahimi, Zakaria Rachid |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Models Molecular Transfection Structure-Activity Relationship chemistry.chemical_compound DU145 Cell Line Tumor Drug Discovery Humans Structure–activity relationship Epidermal growth factor receptor Cytotoxicity Antineoplastic Agents Alkylating biology Cell Cycle DNA Nitrogen mustard In vitro ErbB Receptors Cross-Linking Reagents chemistry Biochemistry Cell culture Nitrogen Mustard Compounds Cancer research biology.protein Molecular Medicine Drug Screening Assays Antitumor Triazenes DNA Damage |
| Zdroj: | Journal of Medicinal Chemistry. 50:2605-2608 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm070144p |
| Popis: | To enhance the potency of "combi-molecules", we designed 6a-d and 18 to release an inhibitor of EGFR TK and a bifunctional alkylator. The combi-molecules blocked EGFR TK with potency increasing with the basicity of the mustard moiety. They selectively killed cells transfected with EGFR and were potent against the DU145 prostate cancer cells. Combi-molecule 6a blocked EGFR phosphorylation in an irreversible manner, induced DNA-cross-links, and arrested the cells in mid-S. |
| Databáze: | OpenAIRE |
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