SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types

Cancer Research

Volumn 59, Issue 1, 1999, Pages 99-106

  Fong, T Annie T ^a,b   Shawver, Laura K ^b   Sun, Li ^b   Tang, Cho ^b   App, Harald ^b   Powell, T Jeff ^b   Kim, Young H ^b   Schreck, Randall ^b   Wang, Xueyan ^b   Risau, Werner ^c   Ullrich, Axel ^d   Hirth, K Peter ^b   McMahon, Gerald ^b  

^a Progenitor Inc   (United States)

^b SUGEN INC   (United States)

^c MAX PLANCK INSTITUTE FOR HEART AND LUNG RESEARCH   (Germany)

^d MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; SEMAXANIB; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR;

ANGIOGENESIS; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CATALYSIS; CELL STRAIN 3T3; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; MITOGENESIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; SUBCUTANEOUS DRUG ADMINISTRATION; TUMOR VASCULARIZATION;

3T3 CELLS; ANIMALS; CATALYSIS; CELL DIVISION; ENDOTHELIUM, VASCULAR; ENZYME INHIBITORS; GLIOMA; HUMANS; INDOLES; MICE; NEOPLASMS, EXPERIMENTAL; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN-TYROSINE KINASES; PYRROLES; RATS; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTORS, GROWTH FACTOR; RECEPTORS, MITOGEN; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; TUMOR CELLS, CULTURED;

EID: 0032893263     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (54)

1. Folkman, J. Anti-angiogenesis: new concept for therapy of solid tumors. Ann. Surg., 175: 409-416, 1972.
2. Risau, W. Mechanisms of angiogenesis. Nature (Lond.), 386: 671-674, 1997.
3. Brem, S., Brem, H., Folkman, J., Finkelstein, D., and Patz, A. Prolonged tumor dormancy by prevention of neovascularization in the vitreous. Cancer Res., 36: 2807-2812, 1976.
4. Holmgren, L., O'Reilly, M. S., and Folkman, J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat. Med., 1: 149-153, 1995.
5. Parangi, S., Dietrih, W., Christofori, G., Lander, E. S., and Hanahan, D. Tumor suppressor loci on mouse chromosomes 9 and 16 are lost at distinct stages of tumorigenesis in a transgenic model of islet cell carcinoma. Cancer Res., 55: 6071-6076, 1995.
6. Gasparini, G., and Harris, A. L. Clinical importance of the determination of tumour angiogenesis in breast carcinoma: much more than a new prognostic tool. J. Clin. Oncol., 13: 765-782, 1995.
7. Toi, M., Hoshina, S., Takayanagi, T., and Tominaga, T. Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn. J. Cancer Res., 85: 1045-1049, 1994.
8. Dickinson, A. J., Fox, S. B., Persad, R. A., Hollyer, J., Sibley, G. N. A., and Harris, A. L. Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas. Br. J. Urol., 74: 762-766, 1994.
9. Takahashi, Y., Kitadai, Y., Bucana, C. D., Cleary, K. R., and Ellis, L. M. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res., 55: 3964-3968, 1995.
10. Williams, J. K., Carlson, G. W., Cohen, C., Derose, P. B., Hunter, S., and Jurkiewicz, M. J. Tumor angiogenesis as a prognostic factor in oral cavity tumours. Am. J. Surg., 168: 373-380, 1994.
11. Shawver, L. K., Lipson, K. E., Fong, T. A. T., McMahon, G., Plowman, G. D., and Strawn, M. Receptor tyrosine kinases as targets for inhibition of angiogenesis. Drug Discovery Today, 2: 50-63, 1997.
12. Millauer, B., Wizigmann-Voos, S., Schnurch, H., Martinez, R., Moller, N. P., Risau, W., and Ullrich, A. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell, 72: 835-846, 1993.
13. Quinn, T. P., Peters, K. G., De Vries, C., Ferrara, N., and Williams, L. T. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc. Natl. Acad. Sci. USA. 90: 7533-7537, 1993.
14. Peters, K., Werner, S., Liao, X., Wert, S., Whitsett, J., and Williams, L. Targeted expression of a dominant negative FGF receptor blocks branching morphogenesis and epithelial differentiation of the mouse lung. EMBO J., 13: 3296-3301, 1994.
15. Shalaby, F., Rossant, J., Yamaguchi, T. P., Gertsenstein, M., Wu, X. F., Breitman, M. L., and Schuh, A. C. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature (Lond.), 376: 62-66, 1995.
16. Fong, G. H., Rossant, J., Gertsenstein, M., and Breitman, M. L. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature (Lond.), 376: 66-70, 1995.
17. Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Gertsenstein, M., Fahrig, M., Vandenhoeck, A., Harpal, K., Eberhardt, C., Declercq, C., Pawling, J., Moons, L., Collen, D., Risau, W., and Nagy, A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature (Lond.), 380: 435-439, 1996.
18. Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O'Shea, K. S., Powell-Braxton, L., Hillan, K. J., and Moore, M. W. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature (Lond.), 380: 439-442, 1996.
19. Plate, K. H., Breier, G., Weich, H. A., and Risau, W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature (Lond.), 359: 845-848, 1992.
20. Plate, K. H., Breier, G., Weich, H. A., Mennel, H. D., and Risau, W. Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. Int. J. Cancer, 59: 520-529, 1994.
21. Yoshiji, H., Gomez, D. E., Shibuya. M., and Thorgeirsson, U. P. Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res., 56: 2013-2016, 1996.
22. O'Brien, T., Cranston, D., Fuggle, S., Bicknell, R., and Harris, A. L. Different angiogenic pathways characterize superficial and invasive bladder cancer. Cancer Res., 55: 510-513, 1995.
23. Shifren, J. L., Tseng, J. F., Zaloudek, C. J., Ryan, I. P., Meng, Y. G., Ferrara, N., Jaffe R. B., and Taylor, R. N. Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J. Clin. Endocrinol. Metab., 81: 3112-3118, 1996.
24. Warren, R. S., Yuan, H., Matli, M. R., Gillett, N. A., and Ferrara, N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J. Clin. Invest., 95: 1789-1797, 1995.
25. Brown, L. F., Berse, B., Jackman, R. W., Tognazzi, K., Manseau, E. J., Senger, D. R., and Dvorak, H. F. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res., 53: 4727-4735, 1993.
26. Anan, K., Morisaki, T., Katano, M., Ikubo, A., Kitsuki, H., Uchiyama, A., Kuroki, S., Tanaka, M., and Torisu, M. Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer. Surgery. 119: 333-339, 1996.
27. Takahashi, A., Sasaki, H., Kim, S. J., Tobisu, K., Kakizoe, T., Tsukamoto, T., Kumamoto, Y., Sugimura, T., and Terada, M. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res., 54: 4233-4237, 1994.
28. Millauer, B., Shawver, L. K., Plate, K. H., Risau, W., and Ullrich, A. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature (Lond.), 367: 576-579, 1994.
29. Millauer, B., Longhi, M. P., Plate, K. H., Shawver, L. K., Risau, W., Ullrich, A., and Strawn, L. M. Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. Cancer Res., 56: 1615-1620, 1996.
30. Salch, M., Stacker, S. A., and Wilks, A. F. Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res., 56: 393-401, 1996.
31. Claffey, K. P., Brown, L. F., del Aguila, L. F., Tognazzi, K., Yeo, K. T., Manseau, E. J., and Dvorak, H. F. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res., 56: 172-181, 1996.
32. Kim, K. J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H. S., and Ferrara, N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature (Lond.), 362: 841-844, 1993.
33. 121. Cancer Res., 55: 5296-5301, 1995.
34. Rockwell, P., Neufeld, G., Glassman, A., Caron, D., and Goldstein, N. In vitro neutralization of vascular endothelial growth factor activation of Flk-1 by a monoclonal antibody. Mol. Cell. Differ., 3: 91-109, 1995.
35. Rockwell, P., Witte, L., Hicklin, D., Pytowski, B., and Goldstein, N. I. Antitumor activity of anti-Flk-1 monoclonal antibodies. Proc. Am. Assc. Cancer Res., 38: 266, 1997.
36. Cushman, C., Escobedo, J., Parry, T. J., Kisich, K. O., Richardson, M. L., Speirer, K. S., Scherrer, J., McSwiggen, J., Maloney, L., DiRenzo, A., Mokier, V. R., Wincott, F. E., and Pavco, P. A. Ribozyme inhibition of VEGF-mediated endothelial cell proliferation in cell culture and VEGF-induced angiogenesis in a rat corneal model. In: Angiogenesis Inhibitors and Other Novel Therapeutic Strategies for Ocular Diseases of Neovascularization, International Business Communications, USA, 1996.
37. Sun, L., Tran, N., Tang, F., App, H., Hirth, P., McMahon, G., and Tang, P. C. Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J. Med. Chem., 41: 2588-2603, 1998.
38. Strawn, L. M., McMahon, G., App, H., Schreck, R., Kuchler, W. R., Longhi, M. P., Hui, T. H., Tang, C., Levitzki, A., Gazit, A., Chen, I., Keri, G., Gift, L., Risau, W., Flamme, I., Ullrich, A., Hirth, K. P., and Shawver, L. K. Flk-1 as a target for tumor growth inhibition. Cancer Res., 56: 3540-3545, 1996.
39. Esser, S., Wolburg, K., Wolburg, H., Breier, G., Kurzchalia, T., and Risau, W. Vascular endothelial growth factor induces endothelial fenestrations in vitro. J. Cell Biol. 140: 947-959, 1998.
40. Shawver, L. K., Schwartz, D. P., Mann, E., Chen, H., Tsai, J., Chu, L., Taylorson, L., Longhi, M., Meredith, S., Germain, L., Jacobs, J. S., Tang, C., Ullrich, A., Berens, M. E., Hersh, E., McMahon, G., Hirth, K. P., and Powell, T. J. Inhibition of platelet-derived growth factor-mediated signal transduction and tumor growth by N-[4-trifluoromethyl)-phenyl]5-methylisoxazole-4-carboxamide. Clin. Cancer Res., 3: 1167-1177, 1997.
41. Skehan, P., Storeng, R., Schudiero, D., Monks, A., McMahon, J., Vistics, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 82: 1107-1112, 1990.
42. Mohammadi, M., McMahon, G., Sun, L., Tang, C., Hirth, P., Yeh, B. K., Hubbard, S. R., and Schlessinger, J. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science (Washington DC), 276: 955-960, 1997.
43. Fry, D. W., Kraker, A. J., McMichael, A., Ambrose, L. A., Nelson, J. M., Leopold, W. R., Connors, R. W., and Bridges, A. J. A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science (Washington DC), 265: 1093-1095, 1994.
44. Brogi, E., Wu, T., Namiki, A., and Isner, J. M. Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only Circulation. 90: 649-652, 1994.
45. Tsai, J-C., Goldman, C. K., and Gillespie, G. Y. Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF. J. Neurosurg., 82: 864-873, 1995.
46. Sundberg, C., Ljungstrom, C., Lindmark, G., Gerdin, B., and Rubin, K. Microvascular pericytes express platelet-derived growth factor-β receptors in human healing wounds and colorectal adenocarcinoma. Am. J. Pathol., 143: 1377-1388, 1993.
47. Sato, N., Beitz, J. G., Kato, J., Yamamoto, M., Clark, J. W., Calabresi, P., and Frackelton, A., Jr. Platelet-derived growth factor indirectly stimulates angiogenesis in vitro. Am. J. Pathol., 142: 1119-1130, 1993.
48. Nicosia, R. F., Nicosia, S. V., and Smith, M. Vascular endothelial growth factor, platelet-derived growth factor and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. Am. J. Pathol., 145: 1023-1029, 1994.
49. Kendall, R. L., and Thomas, K. A. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc. Natl. Acad. Sci. USA. 90: 10705-10709, 1993.
50. Keyt, B. A., Nguyen, H. V., Berleau, L. T., Duarte, C. M., Park, J., Chen, H., and Ferrara, N. Identification of vascular endothelial growth factor determinants for binding KDR and FLT-1 receptors. J. Biol. Chem., 271: 5638-5646, 1996.
51. Clauss, M., Weich, H., Breier, G., Knies, U., Rockl, W., Waltenberger, J., and Risau, W. The vascular endothelial growth factor receptor Flt-1 mediates biological activities. J. Biol. Chem., 30: 17629-17634, 1996.
52. Yoshiji, H., Harris, S. R., and Thorgeirsson, U. P. Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. Cancer Res., 57: 3924-3928, 1997.
53. Bussolino, F., Mantovani, A., and Persico, G. Molecular mechanisms of blood vessel formation. Trends Biochem. Sci., 22: 251-256, 1997.
54. Pluda, J. M. Tumor-associate angiogenesis: mechanisms, clinical implications and therapeutic strategies. Semin. Oncol., 24: 203-218, 1997.