| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
SUGEN, Inc., South San Francisco, CA
Requests for Reprints: Xueyan Wang, 3876 Bay Center Place, Hayward, CA 94545. Phone: (510) 293-8117. E-mail: xwang720{at}yahoo.com
The hepatocyte growth factor/scatter factor (HGF/SF) receptor, Met, mediates various cellular responses on activation with its ligand, including proliferation, survival, motility, invasion, and tubular morphogenesis. Met expression is frequently up-regulated in sarcomas and carcinomas. Experimental evidence suggests that Met activation correlates with poor clinical outcome and the likelihood of metastasis. Therefore, inhibitors of Met tyrosine kinase may be useful for the treatment of a wide variety of cancers that have spread from the primary site. We have discovered potent and selective pyrrole-indolinone Met kinase inhibitors and characterized them for their ability to inhibit HGF/SF-induced cellular responses in vitro. These compounds inhibit HGF/SF-induced receptor phosphorylation in a dose-dependent manner. They also inhibit the HGF/SF-induced motility and invasion of epithelial and carcinoma cells. Therefore, these compounds represent a class of prototype small molecules that selectively inhibit the Met kinase and could lead to identification of compounds with potential therapeutic utility in treatment of cancers.
Grant support: SUGEN, Inc., a subsidiary of Pharmacia Corporation, which was acquired by Pfizer in April 2003.
Received 6/20/03; revised 8/20/03; accepted 8/28/03.
This article has been cited by other articles:
|
|
 |
|
  B. Peruzzi and D. P Bottaro Targeting the c-Met Signaling Pathway in Cancer Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 61 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Shattuck, J. K. Miller, K. L. Carraway III, and C. Sweeney Met Receptor Contributes to Trastuzumab Resistance of Her2-Overexpressing Breast Cancer Cells Cancer Res., March 1, 2008; 68(5): 1471 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Bellon, P. Kaplan-Lefko, Y. Yang, Y. Zhang, J. Moriguchi, K. Rex, C. W. Johnson, P. E. Rose, A. M. Long, A. B. O'Connor, et al. c-Met Inhibitors with Novel Binding Mode Show Activity against Several Hereditary Papillary Renal Cell Carcinoma-related Mutations J. Biol. Chem., February 1, 2008; 283(5): 2675 - 2683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Guo, J. Villen, J. Kornhauser, K. A. Lee, M. P. Stokes, K. Rikova, A. Possemato, J. Nardone, G. Innocenti, R. Wetzel, et al. Signaling networks assembled by oncogenic EGFR and c-Met PNAS, January 15, 2008; 105(2): 692 - 697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M. Linehan, P. A. Pinto, R. Srinivasan, M. Merino, P. Choyke, L. Choyke, J. Coleman, J. Toro, G. Glenn, C. Vocke, et al. Identification of the Genes for Kidney Cancer: Opportunity for Disease-Specific Targeted Therapeutics Clin. Cancer Res., January 15, 2007; 13(2): 671s - 679s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hiscox, N. J Jordan, W. Jiang, M. Harper, R. McClelland, C. Smith, and R. I Nicholson Chronic exposure to fulvestrant promotes overexpression of the c-Met receptor in breast cancer cells: implications for tumour-stroma interactions Endocr. Relat. Cancer, December 1, 2006; 13(4): 1085 - 1099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Cassinelli, C. Lanzi, G. Petrangolini, M. Tortoreto, G. Pratesi, G. Cuccuru, D. Laccabue, R. Supino, S. Belluco, E. Favini, et al. Inhibition of c-Met and prevention of spontaneous metastatic spreading by the 2-indolinone RPI-1. Mol. Cancer Ther., September 1, 2006; 5(9): 2388 - 2397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Strat, L. Gao, T. Utsuki, B. Cheng, S. Nuthalapaty, J. M. Mathis, Y. Odaka, and T. Giordano Specific and nontoxic silencing in mammalian cells with expressed long dsRNAs Nucleic Acids Res., August 11, 2006; 34(13): 3803 - 3810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Peruzzi and D. P. Bottaro Targeting the c-Met Signaling Pathway in Cancer. Clin. Cancer Res., June 15, 2006; 12(12): 3657 - 3660. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
