Small molecule inhibitors of tumor-promoted angiogenesis, including protein tyrosine kinase inhibitors

Pharmacology and Therapeutics

Volumn 82, Issue 2-3, 1999, Pages 169-193

  Hamby, James M ^a   Showalter, H D Hollis ^a  

^a PFIZER INC   (United States)

Author keywords

Angiogenesis; Antiangiogenic; Small molecules; Tyrosine kinase inhibitors

Indexed keywords

2 METHOXYESTRADIOL; ANGIOGENESIS INHIBITOR; ANTIINFLAMMATORY AGENT; ANTINEOPLASTIC AGENT; BATIMASTAT; CALCIUM ANTAGONIST; CURCUMIN; DEXAMETHASONE; FUMAGILLIN; FUMAGILLOL CHLOROACETYLCARBAMATE; LACTACYSTIN; MARIMASTAT; METALLOPROTEINASE INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; ROQUINIMEX; SEMAXANIB; SQUALAMINE; SURAMIN; TETRANDRINE; THALIDOMIDE; TRANILAST; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANGIOGENESIS; ANIMAL MODEL; CARCINOGENESIS; CLINICAL TRIAL; CONFERENCE PAPER; HUMAN; HYPOXIA; MOLECULAR SIZE; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; PRIORITY JOURNAL; SCIENTIFIC LITERATURE; TUMOR VASCULARIZATION;

ANIMALS; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS; HUMANS; LYMPHOCYTE SPECIFIC PROTEIN TYROSINE KINASE P56(LCK); NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN-TYROSINE KINASES;

EID: 0033025957     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0163-7258(98)00053-9     Document Type: Conference Paper

References (188)

1. Algire G.H., Chalkley H.W., Legallis F.Y., Park H.D. Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and normal and neoplastic transplants. J. Natl. Cancer Inst. 6:1946;73-85.
2. Arbiser J.L. Antiangiogenic therapy and dermatology. a review Drugs Today. 33:1997;687-696.
3. Arbiser J.L., Klauber N., Rohan R., Van Leeuwen R., Huang M.-T., Fisher C., Flynn E., Byers H.R. Curcumin is an in vivo inhibitor of angiogenesis. Mol. Med. 4:1998;376-383.
4. Asano M., Yukita A., Matsumoto T., Hanatani M., Suzuki H. An anti-human VEGF monoclonal antibody, MV833, that exhibits potent anti-tumor activity in vivo. Hybridoma. 17:1998;185-190.
5. Augustin H.G. Antiangiogenic tumor therapy. will it work Trends Pharmacol. Sci. 19:1998;216-222.
6. Beckett R.P. Recent advances in the field of matrix metalloproteinase inhibitors. Expert Opin. Ther. Patents. 6:1996;1305-1315.
7. Berlin J., Tutsch K.D., Hutson P., Cleary J., Rago R.P., Arzoomanian R.Z., Alberti D., Feierabend C., Wilding G. Phase I clinical and pharmacokinetic study of oral carboxyamidotriazole, a signal transduction inhibitor. J. Clin. Oncol. 15:1997;781-789.
8. Black W.R., Agner R.C. Tumor regression after endostatin therapy. Nature. 391:1998;450.
9. Boehm T., Folkman J., Browder T., O'Reilly M.S. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature. 390:1997;404-407.
10. Borgstrom P., Bourdon M.A., Hillan K.J., Sriramarao P., Ferrara N. Neutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo. Prostate. 35:1998;1-10.
11. Bouck N., Stellmach V., Hsu S.C. How tumors become angiogenic. Adv. Cancer Res. 69:1996;135-174.
12. Bouvet M., Ellis L.M., Nishizaki M., Fujiwara T., Liu W., Bucana C.D., Fang B., Lee J.J., Roth J.A. Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human colon cancer. Cancer Res. 58:1998;2288-2292.
13. Bramhall S.R. The matrix metalloproteinases and their inhibitors in pancreatic cancer. from molecular science to a clinical application Int. J. Pancreatol. 21:1997;1-12.
14. Brekken R.A., Huang X., King S.W., Thorpe P.E. Vascular endothelial growth factor as a marker of tumor endothelium. Cancer Res. 58:1998;1952-1959.
15. Brem H., Ehrlich H.P., Tsakayannis D., Folkman J. Delay of wound healing by the angiogenesis inhibitor TNP-470. Surg. Forum. 48:1997;714-716.
16. Bridges A.J. Current progress towards the development of tyrosine kinase inhibitors as anticancer agents. Emerging Drugs. 3:1998;279-292.
17. Brooks P.C. Cell adhesion molecules in angiogenesis. Cancer Metastasis Rev. 15:1996;187-194.
18. Brooks, P. and Cheresh, D. A. (1997) Methods and compositions useful for inhibition of angiogenesis. World Patent Application WO 9745447.
19. Brooks P.C., Clark R.A.F., Cheresh D.A. Requirement of vascular integrin αvβ3 for angiogenesis. Science. 264:1994;569-571.
20. Brown J.M. Exploiting tumor hypoxia and overcoming mutant p53 with tirapazamine. Br. J. Cancer. 77:1998;12-14.
21. Bussolino F., Mantovani A., Persico G. Molecular mechanisms of blood vessel formation. Trends Biochem. Sci. 22:1997;251-256.
22. Campbell S.C., Volpert O.V., Ivanovich M., Bouck N.P. Molecular mediators of angiogenesis in bladder cancer. Cancer Res. 58:1998;1298-1304.
23. Castronovo V., Belotti D. TNP-470 (AGM-1470). mechanisms of action and early clinical development Eur. J. Cancer. 32A:1996;2520-2527.
24. Clark A.F. AL-3789. a novel ophthalmic angiostatic steroid Expert Opin. Invest. Drugs. 6:1997;1867-1877.
25. Connolly C.J.C., Hamby J.M., Schroeder M.C., Barvian M., Lu G.H., Panek R.L., Amar A., Shen C., Kraker A.J., Fry D.W., Klohs W.D., Doherty A.M. Discovery and structure-activity studies of a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett. 7:1997;2415-2420.
26. Cowley G., Rogers A. Of mice and men. Newsweek. May 18, 131:1998;58-61.
27. Czubayko F., Liaudet-Coopman E.D.E., Aigner A., Tuveson A.T., Berchem G.J., Wellstein A. A secreted FGF-binding protein can serve as the angiogenic switch in human cancer. Nature Med. 3:1997;1137-1140.
28. D'Amato, R. (1997) Methods and compositions for inhibition of angiogenesis. United States Patent 5629327.
29. D'Amato R.J., Loughnan M.S., Flynn E., Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc. Natl. Acad. Sci. USA. 91:1994;4082-4085.
30. Dameron K.M., Volpert O.V., Tainsky M.A., Bouck N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science. 265:1994;1582-1584.
31. Davidson J.M., Benn S.I. Regulation of angiogenesis and wound repair. Interactive role of the matrix and growth factors. Sirica A.E. Cellular and Molecular Pathogenesis. 1996;79-107 Lippincott-Raven, Philadelphia.
32. Derbyshire E.J., Thorpe P.E. Targeting the tumor endothelium using specific antibodies. Bicknell R.L., Claire E. Tumour Angiogenesis. 1997;343-356 Oxford University Press, Oxford.
33. Dezube B.J., Von Roenn J.H., Holden-Wiltse J., Cheung T.W., Remick S.C., Cooley T.P., Moore J., Sommadossi J.-P., Shriver S.L., Suckow C.W., Gill P.S. Fumagillin analog in the treatment of Kaposi's sarcoma. a phase I AIDS clinical trial group study J. Clin. Oncol. 16:1998;1444-1449.
34. Dimitroff C.J., Klohs W., Sharma A., Pera P., Driscoll D., An C., Veith J., Schroeder M., Klutchko S., Bernacki R.J. Evaluation of the effects of PD166285 and PD173074 on in vitro and in vivo angiogenesis. Proc. Am. Assoc. Cancer Res. 39:1998;96.
35. Ehrmann R.L., Knoth M. Choriocarcinoma. transfilter stimulation of vasoproliferation in the hamster cheek pouch J. Natl. Cancer Inst. 41:1968;1329-1332.
36. Enholm B., Paavonen K., Ristimaki A., Kumar V., Gunji Y., Klefstrom J., Kivinen L., Laiho M., Olofsson B., Joukov V., Eriksson U., Alitalo K. Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene. 14:1997;2475-2483.
37. Ferrara N. The role of vascular endothelial growth factor in the regulation of blood vessel growth. Bicknell R.L., Claire E. Tumour Angiogenesis. 1997;185-199 Oxford University Press, Oxford.
38. Figg W.D., Pluda J.M., Lush R.M., Saville M.W., Wyvill K., Reed E., Yarchoan R. The pharmacokinetics of TNP-470, a new angiogenesis inhibitor. Pharmacotherapy. 17:1997;91-97.
39. Folkman J. Tumor angiogenesis. therapeutic implications N. Engl. J. Med. 285:1971;1182-1186.
40. Folkman J. Anti-angiogenesis. new concept for therapy of solid tumors Ann. Surg. 175:1972;409-416.
41. Folkman J. Tumor angiogenesis. Adv. Cancer Res. 43:1985;175-203.
42. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med. 1:1995;27-31.
43. Folkman J., Klagsbrun M. Angiogenic factors. Science. 235:1987;442-447.
44. Folkman J., Shing Y. Angiogenesis. J. Biol. Chem. 267:1992;10931-10934.
45. Folkman J., Merler E., Abernathy C., Williams G. Isolation of a tumor factor responsible for angiogenesis. J. Exp. Med. 133:1971;275-288.
46. Folkman J., Langer R., Linhardt R.J., Haudenschild C., Taylor S. Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone. Science. 221:1983;719-725.
47. Fong T.A.T., Shawver L.K., App H., Sun L., Tang C., Rice A., Kim Y.H., Schreck R., Chen J., Dowd B., Suto E., Vasile S., Wang X., Hirth K.P., McMahon G. SU5416. a potent and selective Flk-1/KDR kinase inhibitor that blocks Flk-1 phosphorylation, endothelial cell mitogenesis, and tumor growth Proc. Am. Assoc. Cancer Res. 39:1998;560.
48. Fotsis T., Zhang Y., Pepper M.S., Adlercreutz H., Montesano R., Nawroth P.P., Schweigerer L. The endogenous estrogen metabolite 2-methoxyestradiol inhibits angiogenesis and suppresses tumor growth. Nature. 368:1994;237-239.
49. Freskos, J. N., Abbas, Z. S., Decrescenzo, G. A., Getman, D. P., Heintz, R. M., Mischke, B. V. and McDonald, J. J. (1998) Thiol sulfone metalloprotinease inhibitors. World Patent Application WO 9803164.
50. Giannis A., Ruebsam F. Integrin antagonists and other low molecular weight compounds as inhibitors of angiogenesis. new drugs in cancer therapy Angew. Chem. Int. Ed. Engl. 36:1997;588-590.
51. Gorman C. The hope & the hype. Time. May 18, 151:1998;38-44.
52. Gradishar W.J. An overview of clinical trials involving inhibitors of angiogenesis and their mechanism of action. Invest. New Drugs. 15:1997;49-59.
53. Greenblatt M., Shubik P. Tumor angiogenesis. transfilter diffusion studies in the hamster by transparent chamber technique J. Natl. Cancer Inst. 41:1968;111-114.
54. Guichard M., Stern S., Lartigau E. Radioresistance linked to hypoxia. from the cell to the patient J. Chim. Phys. Phys. Chim. Biol. 95:1998;782-787.
55. Gutman M., Szold A., Ravid A., Lazauskas T., Merimsky O., Klausner J.M. Failure of thalidomide to inhibit tumor growth and angiogenesis in vivo. Anticancer Res. 16:1996;3673-3677.
56. Hagmann W.K., Larkk M.W., Becker J.W. Inhibition of matrix metalloproteinases. Annu. Rep. Med. Chem. 31:1996;231-240.
57. Hama Y., Shimizu T., Hosaka S., Sugenoya A., Usuda N. Therapeutic efficacy of the angiogenesis inhibitor O-(chloroacetylcarbamoyl) fumagillol (TNP-470; AGM-1470) for human anaplastic thyroid carcinoma in nude mice. Exp. Toxicol. Pathol. 49:1997;239-247.
58. Hamby J.M., Connolly C.J.C., Schroeder M.C., Winters R.T., Showalter H.D.H., Panek R.L., Major T.C., Olsewski B., Ryan M.J., Dahring T., Lu G.H., Keiser J., Amar A., Shen C., Kraker A.J., Slintak V., Nelson J.M., Fry D.W., Bradford L., Hallak H., Doherty A.M. Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. J. Med. Chem. 40:1997;2296-2303.
59. Hanahan D., Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:1996;353-364.
60. Hanahan D., Christofori G., Naik P., Arbeit J. Transgenic mouse models of tumor angiogenesis. the angiogenic switch, its molecular controls, and prospects for preclinical therapeutic models Eur. J. Cancer. 32A:1996;2386-2393.
61. Hasuike T., Hino M., Yamane T., Nishizawa Y., Morii H., Tatsumi N. Effects of TNP-470, a potent angiogenesis inhibitor, on growth of hematopoietic progenitors. Eur. J. Haematol. 58:1997;293-294.
62. Helmlinger G., Yuan F., Dellian M., Jain R.K. Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nature Med. 3:1997;177-182.
63. Holmgren L., O'Reilly M.S., Folkman J. Dormancy of micrometastases. balanced proliferation and apoptosis in the presence of angiogenesis suppression Nature Med. 1:1995;149-153.
64. Ide A.G., Baker N.H., Warren S.L. Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am. J. Roentgenol. 42:1939;891-899.
65. Ikebe T., Kubo S., Yamamoto T., Goto K., Mikami S., Shuto T., Tsukamoto T., Hirohashi K., Kinoshita H., Kaneda K., Sakurai M. A suppressive effect of an angiogenesis inhibitor TNP-470 on hepatocarcinogenesis in rats. Cells Hepatic Sinusoid. 6:1997;407-410.
66. Ikebe T., Yamamoto T., Kubo S., Hirohashi K., Kinoshita H., Kaneda K., Sakurai M. Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of carcinogen-induced hepatic nodules in rats. Jpn. J. Cancer Res. 89:1998;143-149.
67. Ingber D.E. Discovery of TNP-470 and other angiogenesis inhibitors. Teicher B.A. Cancer Therapeutics. 1997;283-298 Humana, Totowa.
68. Ingber D., Fujita T., Kishimoto S., Sudo K., Kanamaru T., Brem H., Folkman J. Synthetic analogs of fumagillin that inhibit angiogenesis and suppress tumor growth. Nature. 348:1990;555-557.
69. Isaji M., Miyata H., Ajisawa Y., Takehana Y., Yoshimura N. Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo. Br. J. Pharmacol. 122:1997;1061-1066.
70. Jackson J.R., Seed M.P., Kircher C.H., Willoughby D.A., Winkler J.D. The codependence of angiogenesis and chronic inflammation. FASEB J. 11:1997;457-465.
71. Jackson J.R., Bolognese B., Hillegass L., Kassis S., Adams J., Griswold D.E., Winkler J.D. Pharmacological effects of SB 220025, a selective inhibitor of P38 mitogen-activated protein kinase, in angiogenesis and chronic inflammatory disease models. J. Pharmacol. Exp. Ther. 284:1998;687-692.
72. Jang A., Hill R.P. An examination of the effects of hypoxia, acidosis, and glucose starvation on the expression of metastasis-associated genes in murine tumor cells. Clin. Exp. Metastasis. 15:1997;469-483.
73. Jekunen A.P., Kairemo K.J.A. Inhibition of malignant angiogenesis. Cancer Treat. Rev. 23:1997;263-286.
74. Joseph I.B.J.K., Isaacs J.T. Potentiation of the antiangiogenic ability of Linomide by androgen ablation involves down-regulation of vascular endothelial growth factor in human androgen-responsive prostatic cancers. Cancer Res. 57:1997;1054-1057.
75. Kanai T., Konno H., Tanaka T., Matsumoto K., Baba M., Nakamura S., Baba S. Effect of angiogenesis inhibitor TNP-470 on the progression of human gastric cancer xenotransplanted into nude mice. Int. J. Cancer. 71:1997;838-841.
76. Kang S.-M., Maeda K., Onoda N., Chung Y.-S., Nakata B., Nishiguchi Y., Sowa M. Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis. Int. J. Cancer. 74:1997;502-507.
77. Ke L.D., Fueyo J., Chen X., Steck P.A., Shi Y.-X., Im S.-A., Yung W.K.A. A novel approach to glioma gene therapy. down-regulation of the vascular endothelial growth factor in glioma cells using ribozymes Int. J. Oncol. 12:1998;1391-1396.
78. Klauber N., Rohan R.M., Flynn E., D'Amato R.J. Critical components of the female reproductive pathway are suppressed by the angiogenesis inhibitor AGM-1470. Nature Med. 3:1997;443-446.
79. Klein-Soyer C., Ceraline J., Orvain C., de la Salle C., Bergerat J.-P., Cazenave J.-P. Angiogenesis inhibitor SR 25989 upregulates thrombospondin-1 expression in human vascular endothelial cells and foreskin fibroblasts. Biol. Cell. 89:1997;295-307.
80. Klohs W.D., Fry D.W., Kraker A.J. Inhibitors of tyrosine kinase. Curr. Opin. Oncol. 9:1997;562-568.
81. Kobayashi S., Inaba K., Kimura I., Kimura M. Inhibitory effects of tetrandrine on angiogenesis in adjuvant-induced chronic inflammation and tube formation of vascular endothelial cells. Biol. Pharm. Bull. 21:1998;346-349.
82. Kohn E.C., Figg W.D., Sarosy G.A., Bauer K.S., Davis P.A., Soltis M.J., Thompkins A., Liotta L.A., Reed E. Phase I trial of micronized formulation carboxyamidotriazole in patients with refractory solid tumors. pharmacokinetics, clinical outcome, and comparison of formulations J. Clin. Oncol. 15:1997;1985-1993.
83. Kolata, G. (1998) A cautious awe greets drugs that eradicate tumors in mice. New York Times, May 3, Sect. 1: 1.
84. Kolibaba K.S., Druker B.J. Protein tyrosine kinases and cancer. Biochim. Biophys. Acta. 1333:1997;F217-F248.
85. Kong H.-L., Crystal R.G. Gene therapy strategies for tumor antiangiogenesis. J. Natl. Cancer Inst. 90:1998;273-286.
86. Kudelka A.P., Levy T., Verschraegen C.F., Edwards C.L., Piamsomboon S., Termrungruanglert W., Freedman R.S., Kaplan A.L., Kieback D.G., Meyers C.A., Jaeckle K.A., Loyer E., Steger M., Mante R., Mavligit G., Killian A., Tang R.A., Gutterman J.U., Kavanagh J.J. A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. Clin. Cancer Res. 3:1997;1501-1505.
87. Kuiper R.A.J., Schellens J.H.M., Blijham G.H., Beijnen J.H., Voest E.E. Clinical research on antiangiogenic therapy. Pharmacol. Res. 37:1998;1-6.
88. Kumar C., Armstrong L. Tumor-induced angiogenesis. a novel target for drug therapy? Emerging Drugs. 2:1997;175-190.
89. Kusaka M., Sudo K., Fujita T., Marui S., Itoh F., Ingber D., Folkman J. Potent antiangiogenic action of AGM-1470. comparison with the fumagillin parent Biochem. Biophys. Res. Commun. 174:1991;1070-1076.
90. Kusaka M., Sudo K., Matsutani E., Kozai Y., Marui S., Fujita T., Ingber D., Folkman J. Cytostatic inhibition of endothelial cell growth by the angiogenesis inhibitor TNP-470 (AGM-1470). Br. J. Cancer. 69:1994;212-216.
91. Lavelle F. American Association for Cancer Research 1998. promises and prospects for the next century Expert Opin. Invest. Drugs. 7:1998;1015-1021.
92. Lawrence D.S., Niu J. Protein kinase inhibitors. the tyrosine-specific protein kinases Pharmacol. Ther. 77:1998;81-114.
93. Lee K.-E. Influence of chemotherapeutic agents on the proliferation of capillary endothelial cells and tumor angiogenesis in murine bladder cancer. Int. J. Oncol. 6:1995;1021-1026.
94. Lin P., Sankar S., Shan S.-Q., Dewhirst M.W., Polverini P.J., Quinn T.Q., Peters K.G. Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor. Cell Growth Differ. 9:1998;49-58.
95. Lohmann, J-J. M., Hennequin, L. F. A. and Thomas, A. P. (1997) Preparation and antiangiogenic and/or vascular permeability reducing effect of quinazoline derivatives. World Patent Application WO 9722596.
96. Maier J.A.M., Delia D., Thorpe P.E., Gasparini G. in vitro inhibition of endothelial cell growth by the antiangiogenic drug AGM-1470 (TNP-470) and the anti-endoglin antibody TEC-11. Anticancer Drugs. 8:1997;238-244.
97. Marshall E. The power of the front page of the New York Times. Science. 280:1998;996-997. a.
98. Marshall E. The roadblocks to angiogenesis blockers. Science. 280:1998;997. b.
99. Mazure N.M., Chen E.Y., Laderoute K.R., Giaccia A.J. Induction of vascular endothelial growth factor by hypoxia is modulated by phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood. 90:1997;3322-3331.
100. McCarthy M.J., Crowther M., Bell P.R.F., Brindle N.P.J. The endothelial receptor tyrosine kinase tie-1 is up-regulated by hypoxia and vascular endothelial growth factor. FEBS Lett. 423:1998;334-338.
101. Miki T., Nonomura N., Nozawa M., Harada Y., Nishimur K., Kojima Y., Takahara S., Okuyama A. Angiogenesis inhibitor TNP-470 inhibits growth and metastasis of a hormone-independent rat prostatic-carcinoma cell-line. J. Urol. 160:1998;210-213.
102. Millar A.W., Brown P.D., Moore J., Galloway W.A., Cornish A.G., Lenehan T.J., Lynch K.P. Results of single and repeat dose studies of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers. Br. J. Clin. Pharmacol. 45:1998;21-26.
103. Mohammadi M., Froum S., Hamby J.M., Schroeder M.C., Panek R.L., Lu G.H., Eliseenkova A.V., Green D., Schlessinger J., Hubbard S.R. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 17:1998;5896-5904.
104. Molema G., de Leij L.F.M.H., Meijer D.K.F. Tumor vascular endothelium. barrier or target in tumor directed drug delivery and immunotherapy Pharm. Res. 14:1997;2-10.
105. Molema G., Meijer D.K.F., De Leij L.F.M.H. Tumor vasculature targeted therapies. Getting the players organized. Biochem. Pharmacol. 55:1998;1939-1945.
106. Moller P.H., Ivarsson K., Roos G., Radnell M., Persson B., Tranberg K.-G., Stenram U. Angiogenesis inhibitor TNP-470 augments the effect of repeated arterial ischemia on growth but does not affect take in a rat liver tumor model. Anticancer Res. 17:1997;2401-2406.
107. Mori S., Yoshikawa H., Hashimoto J., Ueda T., Funai H., Kato M., Takaoka K. Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Bone. 22:1998;99-105.
108. Morris A.D., Leonce S., Guilbaud N., Tucker G.C., Perez V., Jan M., Cordi A.A., Pierre A., Atassi G. Eriochrome Black T, structurally related to suramin, inhibits angiogenesis and tumor growth in vivo. Anticancer Drugs. 8:1997;746-755.
109. Myers M.R., He W., Hulme C. Inhibitors of tyrosine kinases involved in inflammation and autoimmune disease. Curr. Pharm. Design. 3:1997;473-502.
110. Mysliwski A., Szmit E., Szatkowski D., Sosnowska D. Suppression of growth of Bomirski Ab melanoma and its metastasis in hamsters by angiogenesis inhibitor TNP-470. Anticancer Res. 18:1998;441-443.
111. Nagler A., Feferman R., Shoshan S. Reduction in basic fibroblast growth factor mediated angiogenesis in vivo by linomide. Connect. Tissue Res. 37:1998;61-68.
112. Nauck M., Karakiulakis G., Perruchoud A.P., Papakonstantinou E., Roth M. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur. J. Pharmacol. 341:1998;309-315.
113. Nguyen M., Tran C., Barsky S., Sun J.-R., Mcbride W., Pegram M., Pietras R., Love S., Glaspy J. Thalidomide and chemotherapy combination. preliminary results of preclinical and clinical studies Int. J. Oncol. 10:1997;965-969.
114. Norrby K. Angiogenesis. new aspects relating to its initiation and control APMIS. 105:1997;417-437.
115. Ohta Y., Watanabe Y., Tabata T., Oda M., Hayashi Y., Endo Y., Tanaka M., Sasaki T. Inhibition of lymph node metastasis by an anti-angiogenic agent, TNP-470. Br. J. Cancer. 75:1997;512-515.
116. Oikawa T., Sasaki M., Inose M., Shimamura M., Kuboki H., Hirano S.-I., Kumagai H., Ishizuka M., Takeuchi T. Effects of cytogenin, a novel microbial product, on embryonic and tumor cell-induced angiogenic responses in vivo. Anticancer Res. 17:1997;1881-1886.
117. Oikawa T., Sasaki T., Nakamura M., Shimamura M., Tanahashi N., Omura S., Tanaka K. The proteasome is involved in angiogenesis. Biochem. Biophys. Res. Commun. 246:1998;243-248.
118. Okada F., Rak J.W., Croix B.S., Lieubeau B., Kaya M., Roncari L., Shirasawa S., Sasazuki T., Kerbel R.S. Impact of oncogenes in tumor angiogenesis. mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells Proc. Natl. Acad. Sci. USA. 95:1998;3609-3614.
119. Oliver S.J., Cheng T.P., Banquerigo M.L., Brahn E. The effect of thalidomide and 2 analogs on collagen induced arthritis. J. Rheumatol. 25:1998;964-969.
120. Or R., Feferman R., Shoshan S. Thalidomide reduces vascular density in granulation tissue of subcutaneously implanted polyvinyl alcohol sponges in guinea pigs. Exp. Hematol. 26:1998;217-221.
121. O'Reilly M.S. Angiostatin. an endogenous inhibitor of angiogenesis and of tumor growth EXS. 79:1997;273-294.
122. O'Reilly M.S., Holmgren L., Shing Y., Chen C., Rosenthal R.A., Cao Y., Moses M., Lane W.S., Sage E.H., Folkman J. Angiostatin. a circulating endothelial cell inhibitor that suppresses angiogenesis and tumor growth Cold Spring Harbor Symp. Quant. Biol. 59:1994;471-482. a.
123. O'Reilly M.S., Holmgren L., Shing Y., Chen C., Rosenthal R.A., Moses M., Lane W.S., Cao Y., Sage E.H., Folkman J. Angiostatin. a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma Cell. 79:1994;315-328. b.
124. O'Reilly M.S., Holmgren L., Chen C., Folkman J. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nature Med. 2:1996;689-692.
125. O'Reilly M.S., Boehm T., Shing Y., Fukai N., Vasios G., Lane W.S., Flynn E., Birkhead J.R., Olsen B.R., Folkman J. Endostatin. an endogenous inhibitor of angiogenesis and tumor growth Cell. 88:1997;277-285.
126. Panek R.L., Lu G.H., Dahring T.K., Batley B.L., Connolly C., Hamby J.M., Brown K.J. in vitro biological characterization and antiangiogenic effects of PD 166866, a selective inhibitor of the FGF-1 receptor tyrosine kinase. J. Pharmacol. Exp. Ther. 286:1998;569-577.
127. Pepper M.S., Vassalli J.-D., Orci L., Montesano R. Angiogenesis in vitro: cytokine interactions and balanced extracellular proteolysis. Maragoudakis M.E., Gullino P.M., Lekles P.I. Angiogenesis. Molecular Biology, Clinical Aspects:1994;149-170 Plenum Press, New York.
128. Pepper M.S., Montesano R., Mandriota S.J., Orci L., Vassalli J.-D. Angiogenesis. a paradigm for balanced extracellular proteolysis during cell migration and morphogenesis Enzyme Protein. 49:1996;138-162.
129. Petit A.M.V., Rak J., Hung M.-C., Rockwell P., Goldstein N., Fendly B., Kerbel R.S. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am. J. Pathol. 151:1997;1523-1530.
130. Pluda J.M. Tumor-associated angiogenesis. mechanisms, clinical implications, and therapeutic strategies Semin. Oncol. 24:1997;203-218.
131. Pollard M. Effects of linomide on advanced prostate-seminal vesicle cancers in Lobund-Wistar rats. Prostate. 35:1998;43-49.
132. Polverini P.J. How the extracellular matrix and macrophages contribute to angiogenesis-dependent diseases. Eur. J. Cancer. 32A:1997;2430-2437.
133. Powell D., Skotnicki J., Upeslacis J. Angiogenesis inhibitors. Annu. Rep. Med. Chem. 32:1997;161-170.
134. Powell W.C., Matrisian L.M. Complex roles of matrix metalloproteinases in tumor progression. Curr. Top. Microbiol. Immunol. 213:1996;1-21.
135. Rak J., Kerbel R.S. Basic fibroblast growth factor and the complexity of tumor angiogenesis. Expert Opin. Invest. Drugs. 7:1998;797-801.
136. Rasmussen H.S., McCann P.P. Matrix metalloproteinase inhibition as a novel anticancer strategy. a review with special focus on batimastat and marimastat Pharmacol. Ther. 75:1997;69-75.
137. Ray J.M., Stetler-Stevenson W.G. The role of matrix metalloproteases and their inhibitors in tumor invasion, metastasis and angiogenesis. Eur. Respir. J. 7:1994;2062-2072.
138. Ray S., Dwivedy I. Development of estrogen antagonists as pharmaceutical agents. Adv. Drug Res. 29:1997;171-270.
139. Reynolds R.P., Redmer D. Expression of the angiogenic factors, basic fibroblast growth factor and vascular endothelial growth factor. J. Anim. Sci. 76:1998;1671-1681.
140. Risau W. Angiogenic growth factor. Prog. Growth Factor Res. 2:1990;71-79.
141. Rofstad E.K., Danielsen T. Hypoxia-induced angiogenesis and vascular endothelial growth factor secretion in human melanoma. Br. J. Cancer. 77:1998;897-902.
142. Rosen L.S., Kabbinavar F., Rosen P., Mulay M., Quigley S., Hannah A.L. Phase I trial of SU5416, a novel angiogenesis inhibitor in patients with advanced malignancies. Proc. Am. Soc. Clin. Oncol. 17:1998;218a.
143. Royds J.A., Dower S.K., Qwarnstrom E.E., Lewis C.E. Response of tumor cells to hypoxia. role of p53 and NFkB Mol. Pathol. 51:1998;55-61.
144. Santos O., Mcdermott C.D., Daniels R.G., Appelt K. Rodent pharmacokinetic and anti-tumor efficacy studies with a series of synthetic inhibitors of matrix metalloproteinases. Clin. Exp. Metastasis. 15:1997;499-508.
145. Sasaki A., Alcalde R.E., Nishiyama A., Lim D.D., Mese H., Akedo H., Matsumura T. Angiogenesis inhibitor TNP-470 inhibits human breast cancer osteolytic bone metastasis in nude mice through the reduction of bone resorption. Cancer Res. 58:1998;462-467.
146. Schweiger E.J., Joullie M.M., Weisz P.B. Synthesis of a CD-ring analog of 17 α-hydroxyprogesterone. Tetrahedron Lett. 38:1997;6127-6130.
147. Scott P.A.E., Gleadle J.M., Bicknell R., Harris A.L. Role of the hypoxia sensing system, acidity and reproductive hormones in the variability of vascular endothelial growth factor induction in human breast carcinoma cell lines. Int. J. Cancer. 75:1998;706-712.
148. Seedorf K. Intracellular signaling by growth factors. Metab. Clin. Exp. 44(Suppl. 4):1995;24-32.
149. Sekido Y., Fong K.M., Minna J.D. Progress in understanding the molecular pathogenesis of human lung cancer. Biochim. Biophys. Acta. 1378:1998;F21-F59.
150. Shawver L.K., Lipson K.E., Fong T.A.T., McMahon G., Plowman G.D., Strawn L.M. Receptor tyrosine kinases as targets for inhibition of angiogenesis. Drug Discov. Today. 2:1997;50-63.
151. Sheibani N., Frazier W.A. Thrombospondin 1 expression in transformed endothelial cells restores a normal phenotype and suppresses their tumorigenesis. Proc. Natl. Acad. Sci. USA. 92:1995;6788-6792.
152. Shing Y., Folkman J., Sullivan R., Butterfield C., Murray J., Klagsbrun M. Heparin affinity. purification of a tumor-derived capillary endothelial cell growth factor Science. 223:1984;1296-1299.
153. Showalter H.D.H., Kraker A.J. Small molecule inhibitors of the platelet-derived growth factor receptor, the fibroblast growth factor receptor, and Src family tyrosine kinases. Pharmacol. Ther. 76:1997;55-71.
154. Sills A.K. Jr., Williams J.I., Tyler B.M., Epstein D.S., Sipos E.P., Davis J.D., Mclane M.P., Pitchford S., Cheshire K., Gannon F.H., Kinney W.A., Chao T.L., Donowitz M., Laterra J., Zasloff M., Brem H. Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature. Cancer Res. 58:1998;2784-2792.
155. Singh Y., Shikata N., Kiyozuka Y., Nambu H., Morimoto J., Kurebayashi J., Hioki K., Tsubura A. Inhibition of tumor growth and metastasis by angiogenesis inhibitor TNP-470 on breast cancer cell lines in vitro and in vivo. Breast Cancer Res. Treat. 45:1997;15-27.
156. Soltis M.J., Yeh H.J., Cole K.A., Whittaker N., Wersto R.P., Kohn E.C. Identification and characterization of human metabolites of CAI [5-amino-1-(4′-chlorobenzoyl-3,5-dichlorobenzyl)-1,2,3-triazole-4- carboxamide]. Drug Metab. Dispos. 24:1996;799-806.
157. Sternberg S., Manning A. Cancer war may have new weapon. USA Today. May 4,(Sect. A):1998;1.
158. Strawn L.M., Shawver L.K. Tyrosine kinases in disease. overview of kinase inhibitors as therapeutic agents and current drugs in clinical trials Expert Opin. Invest. Drugs. 7:1998;553-573.
159. Sun L., Tran N., Tang F., App H., Hirth P., McMahon G., Tang 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. 41:1998;2588-2603. a.
160. Sun, L., Tran, N., Tang, F., Schreck, R., Annie, T., Fong, T., McMahon, G. and Tang, C. (1998b) Synthesis and biological evaluation of novel 3-(substituted pyrrol-2-yl)indolin-2-ones as potent and selective inhibitors of the Flk-1/KDR receptor tyrosine kinase. In: Abstracts of the 215th American Chemical Society National Meeting, Dallas, March 29-April 2, p. MEDI-169, American Chemical Society, Washington, DC.
161. Tanaka Y., Kawamata H., Fujimoto K., Oyasu R. Angiogenesis inhibitor TNP-470 suppresses tumorigenesis in rat urinary bladder. J. Urol. 157:1997;683-688.
162. Tang, C., Li, S., Tran, J., Liang, C., Nematalla, A., Fong, A., App, H., Rice, A., Kim, Y., Schreck, R., Chen, J., Dowd, B., Suto, E., Vasile, S., Shawver, L., McMahon, J. and Hirth, P. (1998) SU5416: a potent and selective Flk-1/KDR kinase inhibitor that blocks receptor autophosphorylation, endothelial cell mitogenesis, and tumor growth. In: Abstracts of the 215th American Chemical Society National Meeting, Dallas, March 29-April 2, p. MEDI-205, American Chemical Society, Washington, DC.
163. Teicher B.A. A systems approach to cancer therapy. (Antiangiogenics + standard cytotoxics → mechanism(s) of interaction). Cancer Metastasis Rev. 15:1996;247-272.
164. Thomas, A. P., Hennequin, L. F. A. and Johnstone, C. (1997a) Preparation of 4-anilinoquinazolines for use in the treatment of disease states associated with antiangiogenesis and/or increased vascular permeability. World Patent Application WO 9732856.
165. Thomas, A. P., Johnstone, C. and Hennequin, L. F. A. (1997b) Preparation of quinazolines as VEGF inhibitors. World Patent Application WO 9730035.
166. Thomas, A. P., Hennequin, L. F. A. and Ple, P. A. (1998) Quinoline derivatives inhibiting the effect of growth factors such as VEGF. World Patent Application WO 9813350.
167. Traxler P.M. Protein tyrosine kinase inhibitors in cancer treatment. Expert Opin. Ther. Patents. 7:1997;571-588.
168. Trumpp-Kallmeyer S., Rubin J.R., Humblet C., Hamby J.M., Showalter H.D.H. Development of a binding model to protein tyrosine kinases for substituted pyrido[2,3-d]pyrimidine inhibitors. J. Med. Chem. 41:1998;1752-1763.
169. Twardowski P., Gradishar W.J. Clinical trials of antiangiogenic agents. Curr. Opin. Oncol. 9:1997;584-589.
170. Virchow R. Die Krankhaften Geschwulste. 1863;Hirschwald, Berlin.
171. Vlodavsky I., Folkman J., Sullivan R., Fridman R., Ishai-Michaeli R., Sasse J., Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor. synthesis and deposition into subendothelial extracellular matrix Proc. Natl. Acad. Sci. USA. 84:1987;2292-2296.
172. Voest E.E. Inhibitors of angiogenesis in a clinical perspective. Anticancer Drugs. 7:1996;723-727.
173. Volpert O.V., Dameron K.M., Bouck N. Sequential development of an angiogenic phenotype by human fibroblasts progressing to tumorgenicity. Oncogene. 14:1997;1495-1502.
174. Wang Y., Becker D. Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nature Med. 3:1997;887-893.
175. Wassberg E., Poahlman S., Westlin J.-E., Christofferson R. The angiogenesis inhibitor TNP-470 reduces the growth rate of human neuroblastoma in nude rats. Pediatr. Res. 41:1997;327-333.
176. Weinberg R.A. How cancer arises. Sci. Am. 275:1996;62-70.
177. Weinstat-Saslow D.L., Zabrenetzky V.S., VanHoutte K., Frazier W.A., Roberts D.D., Steeg P.S. Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis. Cancer Res. 54:1994;6504-6511.
178. Wojtowicz-Praga S., Torri J., Johnson M., Steen V., Marshall J., Ness E., Dickson R., Sale M., Rasmussen H.S., Chiodo T.A., Hawkins M.J. Phase I trial of marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer. J. Clin. Oncol. 16:1998;2150-2156.
179. Wu Y., Palad A.J., Wasilenko W.J., Blackmore P.F., Pincus W.A., Schechter G.L., Spoonster J.R., Kohn E.C., Somers K.D. Inhibition of head and neck squamous cell carcinoma growth and invasion by the calcium influx inhibitor carboxyamido-triazole. Clin. Cancer Res. 3:1997;1915-1921.
180. Xia J.L., Yang B.H., Tang Z.Y., Sun F.X., Xue Q., Gao D.M. Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma. J. Cancer Res. Clin. Oncol. 123:1997;383-387.
181. Yamamoto S., Konishi I., Tsuruta Y., Nanbu K., Mandai M., Kuroda H., Matsushita K., Hamid A.A., Yura Y., Mori T. Expression of vascular endothelial growth factor (VEGF) during folliculogenesis and corpus luteum formation in the human ovary. Gynecol. Endocrinol. 11:1997;371-381.
182. Yoneda J., Kuniyasu H., Crispens M.A., Price J.E., Bucana C.D., Fidler I.J. Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J. Natl. Cancer Inst. 90:1998;447-454.
183. Young S.D., Marshall R.S., Hill R.P. Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. Proc. Natl. Acad. Sci. USA. 85:1988;9533-9537.
184. Yue T.-L., Wang X., Louden C.S., Gupta S., Pillarisetti K., Gu J.-L., Hart T.K., Lysko P.G., Feuerstein G.Z. 2-Methoxyestradiol, an endogenous estrogen metabolite, induces apoptosis in endothelial cells and inhibits angiogenesis. possible role for stress-activated protein kinase signaling pathway and Fas expression Mol. Pharmacol. 51:1997;951-962.
185. Zask A., Levin J.I., Killar L.M., Skotnicki J.S. Inhibition of matrix metalloproteinases. structure based design Curr. Pharm. Design. 2:1996;624-661.
186. Zetter B.R. Angiogenesis and tumor metastasis. Annu. Rev. Med. 49:1998;407-424.
187. Ziche M., Donnini S., Morbidelli L., Parenti A., Gasparini G., Ledda F. Linomide blocks angiogenesis by breast carcinoma vascular endothelial growth factor transfectants. Br. J. Cancer. 77:1998;1123-1129.
188. Zook, S. E., Dagnino, R. J., Deason, M. E., Bender, S. L. and Melnick, M. J. (1997) Metalloproteinase inhibitors. Pharmaceutical compositions containing them and their pharmaceutical uses, and methods and intermediates useful for their preparation. World Patent Application WO 9720824.