ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy.
作者： Jim R Woodburn , Susan E Ashton , Simon P Guy , Keith H Gibson , Brenda J Curry
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摘要: The epidermal growth factor receptor (EGFR) is a promising target for anticancer therapy because of its role in tumor growth, metastasis and angiogenesis, resistance to chemotherapy radiotherapy. We have developed low-molecular-weight EGFR tyrosine kinase inhibitor (EGFR-TKI), ZD1839 (Iressa(2) ). ZD1839, substituted anilinoquinazoline, potent EGFR-TKI (IC(50) = 0.033 micro M) that selectively inhibits EGF-stimulated cell 0.054 blocks autophosphorylation cells. In studies with mice bearing range human tumor-derived xenografts, given p.o. once day inhibited dose-dependent manner. level expression did not determine xenograft sensitivity ZD1839. Long-term (>3 months) treatment A431 xenografts was well tolerated, completely induced regression established tumors. No drug-resistant tumors appeared during treatment, but some regrew after drug withdrawal. These indicate the potential utility many continuous once-a-day dosing might be suitable therapeutic regimen.
aacrjournals.org参考文章(22)
Dario R. Alessi, Philip Cohen, Alan Ashworth, Sally Cowley, Sally J. Leevers, Christopher J. Marshall, Assay and expression of mitogen-activated protein kinase, MAP kinase kinase, and Raf. Methods in Enzymology. ,vol. 255, pp. 279- 290 ,(1995) , 10.1016/S0076-6879(95)55031-3
Mark M. Moasser, Steven D. Averbuch, Neal Rosen, Andrea Basso, The Tyrosine Kinase Inhibitor ZD1839 ("Iressa") Inhibits HER2-driven Signaling and Suppresses the Growth of HER2-overexpressing Tumor Cells Cancer Research. ,vol. 61, pp. 7184- 7188 ,(2001)
Walter H.J. Ward, Peter N. Cook, Anthony M. Slater, D.Huw Davies, Geoffrey A. Holdgate, Leslie R'. Green, Epidermal growth factor receptor tyrosine kinase: Investigation of catalytic mechanism, structure-based searching and discovery of a potent inhibitor Biochemical Pharmacology. ,vol. 48, pp. 659- 666 ,(1994) , 10.1016/0006-2952(94)90042-6
Mark G. Kris, Howard I. Scher, Vincent A. Miller, Maureen F. Zakowski, Francis M. Sirotnak, Efficacy of Cytotoxic Agents against Human Tumor Xenografts Is Markedly Enhanced By Coadministration of ZD1839 (Iressa), an Inhibitor of EGFR Tyrosine Kinase Clinical Cancer Research. ,vol. 6, pp. 4885- 4892 ,(2000)
Laurent F. Hennequin, Andrew P. Thomas, Craig Johnstone, Elaine S. E. Stokes, Patrick A. Plé, Jean-Jacques M. Lohmann, Donald J. Ogilvie, Mike Dukes, Steve R. Wedge, Jon O. Curwen, Jane Kendrew, Christine Lambert-van der Brempt, Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. Journal of Medicinal Chemistry. ,vol. 42, pp. 5369- 5389 ,(1999) , 10.1021/JM990345W
Jeff B Smaill, Brian D Palmer, Gordon W Rewcastle, William A Denny, Dennis J McNamara, Ellen M Dobrusin, Alexander J Bridges, Hairong Zhou, HD Hollis Showalter, R Thomas Winters, Wilbur R Leopold, David W Fry, James M Nelson, Veronika Slintak, William L Elliot, Billy J Roberts, Patrick W Vincent, Sandra J Patmore, None, Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor. Journal of Medicinal Chemistry. ,vol. 42, pp. 1803- 1815 ,(1999) , 10.1021/JM9806603
A E Wakeling, A J Barker, D H Davies, D S Brown, L R Green, S A Cartlidge, J R Woodburn, New targets for therapeutic attack Endocrine-related Cancer. ,vol. 4, pp. 351- 355 ,(1997) , 10.1677/ERC.0.0040351
Richard A. McClelland, Denise Barrow, Tracie-Ann Madden, Carol M. Dutkowski, Joanna Pamment, Janice M. Knowlden, Julia M. W. Gee, Robert I. Nicholson, Enhanced epidermal growth factor receptor signaling in MCF7 breast cancer cells after long-term culture in the presence of the pure antiestrogen ICI 182,780 (Faslodex). Endocrinology. ,vol. 142, pp. 2776- 2788 ,(2001) , 10.1210/ENDO.142.7.8259
J.R Woodburn, The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacology & Therapeutics. ,vol. 82, pp. 241- 250 ,(1999) , 10.1016/S0163-7258(98)00045-X
P. Yaish, A. Gazit, C. Gilon, A. Levitzki, Blocking of EGF-Dependent Cell Proliferation by EGF Receptor Kinase Inhibitors Science. ,vol. 242, pp. 933- 935 ,(1988) , 10.1126/SCIENCE.3263702