The discovery and development of the combretastatins

Anticancer Agents from Natural Products

Volumn , Issue , 2005, Pages 23-46

  Pinney, Kevin G ^a   Jelinek, Christopher ^a   Edvardsen, Klaus ^b   Chaplin, David J ^c   Pettit, George R ^d  

^a BAYLOR UNIVERSITY   (United States)

^b LUND UNIVERSITY   (Sweden)

^c OXiGENE Inc   (United States)

^d ARIZONA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DISEASES; PLANTS (BOTANY);

DECIDUOUS TREES; EXPLORATORY SURVEYS; LYMPHOCYTIC LEUKEMIA; MEDICAL TREATMENT; NATIONAL CANCER INSTITUTE; PLANT FAMILIES; TERRESTRIAL PLANTS; WOUND DRESSINGS;

FORESTRY;

EID: 85008389252     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (172)

1. Willis, J.C. and Arey Shaw, H.K., A Dictionary of the Flowering Plants & Ferns, 8th ed., Cambridge University Press, London, 1973.
2. Watt, J.M. and Breyer-Brandwijk, M.G., The Medicinal and Poisonous Plants of Southern and Eastern Africa, 2nd ed., E. and S. Livingston, London, 1962, 194.
3. Hartwell, J.L., Plants Used Against Cancer, Quarterman Publications, Laurence, MA, 1982, 108.
4. Wall, M.E. et al., Plant antitumor agents. 3. A convenient separation of tannins from other plant constituents, J. Pharm. Sci., 58, 839, 1969.
5. Palmer, E. and Pitman, N, Trees of Southern Africa, A.A. Balkema, Cape Town, 1972, Vol. 3.
6. Kokwaro, O., Medicinal Plants of East Africa, East African Literature Bureau, Nairobi, 1976.
7. Samuelsson, G. et al., Inventory of plants used in traditional medicine in Somalia. II. Plants of the families combretaceae to labiatae, J. Ethnopharm., 37, 47, 1992.
8. Iwu, M.M., Handbook of African Medicinal Plants, CRC Press, Boca Raton, FL, 1993.
9. Gurib-Fakim, A. and Brendler, T., Medicinal and Aromatic Plants of Indian Ocean Islands: Madagascar, Comoros, Seychelles, and Mascarenes, Medpharm Scientific Publishers, Stuttgart, Germany, 2004, 194, 463.
10. Duke, J., Medicinal Herbs, 2nd ed., CRC Press, New York, 2002, 539.
11. Pettit, G.R. et al., Antineoplastic agents 338. The cancer cell growth inhibitory. Constituents of terminalia arjuna (combretaceae), J. Ethnopharm., 53, 57, 1996.
12. Chinemana, F. et al., Indigenous plant remedies in Zimbabwe, J. Ethnopharm., 14, 159, 1985.
13. Cushman, M. et al., Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization, J. Med. Chem., 34, 2579, 1991.
14. Sackett, D.L., Podophyllotoxin, steganacin, and combretastatin: natural products that bind at the colchicine site of tubulin, Pharm. Ther., 59, 163, 1993.
15. Tozer, G.M. et al., The biology of the combretastatins as tumour vascular targeting agents. Int. J. Exp. Path., 83, 21, 2002.
16. Lin, C.M. et al., Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study, Mol. Pharm., 34, 200, 1988.
17. Li, Q. and Sham, H.L., Discovery and development of antimitotic agents that inhibit tubulin polymerization for the treatment of cancer, Exp. Opin. Ther. Pat., 12, 1663, 2002.
18. Rowinsky, E.K. et al., Horizons in cancer therapeutics: from bench to bedside, Continuing Education, 3, 1, 2002.
19. Hamel, E., Antimitotic natural products and their interactions with tubulin, Med. Res. Rev., 16, 207, 1996.
20. Thorpe, P.E., Vascular targeting agents as cancer therapeutics, Clin. Cancer Res., 10, 415, 2004.
21. Griggs, J., Metcalfe, J.C., and Hesketh, R., Targeting tumour vasculature: the development of combretastatin A4, Lancet Onc., 2, 82, 2001.
22. Bibby, M.C., Combretastatin anticancer drugs, Drugs of the Future, 27, 475, 2002.
23. Cirla, A. and Mann, J., Combretastatins: from natural products to drug discovery, Nat. Prod. Rep., 20, 558, 2003.
24. Nam, N-H., Combretastatin A-4 analogues as antimitotic antitumor agents, Curr. Med. Chem., 10, 1697, 2003.
25. Pettit, G.R. and Lippert, J.W., Preparation of combretastatin A-1 phosphate and combretastatin B-1 phosphate prodrugs with increased solubility, PCT Int. Application WO2001081355 A1, 2001.
26. Pettit, G.R. and Minardi, M.D., Preparation of combretastatin A3 diphosphate prodrugs for the treatment of cancer, PCT Int. Application WO2002102766 A2, 2002.
27. Pettit, G.R. and Singh, S.B, Combretastatin A-4, US Patent 4,996,237, 1991.
28. Pettit, G.R. and Singh, S.B., Isolation, structural elucidation and synthesis of novel antineoplastic substances denominated “combretastatins,” US Patent 5,569,786, 1996.
29. Pettit, G. R., Combretastatin A-4 prodrug, US Patent 5,561,122, 1996.
30. Pinney, K. G. et al., Description of anti-mitotic agents which inhibit tubulin polymerization, US Patent 6,350,777, 2000.
31. Pettit, G.R. and Grealish, M.P., Synthesis of hydroxyphenstatin and the prodrugs thereof as anticancer and antimicrobial agents, PCT Int. Application WO2001081288 A1, 2001.
32. Pettit, G.R. and Brian, T., Synthesis and formulation of phenstatin and related prodrugs for use as antitumor agents, PCT Int. Application WO9934788 A1, 1999.
33. Pettit, G.R. and Rhodes, M.R., Preparation and formulation of combretastatin A4 prodrugs and their trans-isomers for use as antitumor agents, PCT Int. Application WO9935150 A1, 1999.
34. Pettit, G.R. and Moser, B.R., Preparation of combretastatin A-2 prodrugs as antitumor and antimicrobial agents, PCT Int. Application WO2003059855 A1, 2003.
35. Kingston, D.G.I., Samaranayake, G., and Ivey, C.A., The chemistry of taxol, a clinically useful anticancer agent, J. Nat. Prod., 53, 1, 1990.
36. Nicolaou, K.C. et al., Synthesis of epothilones A and B in solid and solution phase, Nature, 387, 268, 1997.
37. Owellen, R.J. et al., Inhibition of tubulin-microtubule polymerization by drugs of the vinca alkaloid class, Cancer Res., 36, 1499, 1976.
38. Pettit, G.R. et al., The isolation and structure of a remarkable marine animal antineoplastic constituent: dolastatin 10, J. Am. Chem. Soc., 109, 6883, 1987.
39. Pettit, G.R. et al., Antineoplastic agents 365. Dolastatin 10 SAR probes, Anticancer Drug Des., 13, 243, 1998.
40. Lin, C.M. et al., Antimitotic natural products combretastatin A-4 and combretastatin A-2: studies on the mechanism of their inhibition of the binding of colchicine to tubulin, Biochemistry, 28, 6984, 1989.
41. Chaplin, D.J., Pettit, G.R., and Hill, S.A., Anti-vascular approaches to solid tumor therapy: evaluation of combretastatin A4 phosphate, Anticancer Res., 19, 189, 1999.
42. Jordon, A. et al., Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle, Med. Res. Rev., 18, 259, 1998.
43. Pinney, K.G. et al., A new anti-tubulin agent containing the benzo[b]thiophene ring system, Bioorg. Med. Chem. Lett., 9, 1081, 1999.
44. Pettit, G.R. and Lippert, J.W., Antineoplastic agents 429. Syntheses of the combretastatin A-1 and combretastatin B-1 prodrugs, Anticancer Drug Des., 15, 203, 2000.
45. Pettit, G.R. et al., Antineoplastic agents 322. Synthesis of combretastatin A-4 prodrugs, Anticancer Drug Des., 10, 299, 1995.
46. Pettit, G.R. et al., Isolation and structure of combretastatin, Can. J. Chem., 60, 1374, 1982.
47. Pettit, G.R., Cragg, G.M., and Singh, S.B., Antineoplastic agents, 122. Constituents of Combretum caffrum, J. Nat. Prod., 50, 386, 1987.
48. Pettit, G.R. et al., Isolation, structure, and synthesis of combretastatins A-1 and B-1, potent new inhibitors of microtubule assembly, derived from Combretum caffrum, J. Nat. Prod., 50, 119, 1987.
49. Pettit, G.R. and Singh, S.B., Isolation, structure, and synthesis of combretastatin A-2, A-3, and B-2, Can. J. Chem., 65, 2390, 1987.
50. Pettit, G.R. et al., Antineoplastic agents. 291. Isolation and synthesis of combretastatins A-4, A-5, and A-6, J. Med. Chem., 38, 1666, 1995.
51. Pettit, G.R., Singh, S.B., and Schmidt, J.M., Isolation, structure, synthesis, and antimitotic properties of combretastatins B-3 and B-4 from Combretum caffrum, J. Nat. Prod., 51, 517, 1988.
52. Singh, S.B. and Pettit, G.R., Isolation, structure, and synthesis of combretastatin C-1, J. Org. Chem., 54, 4105, 1989.
53. Pettit, G.R., Singh, S.B., and Niven, M.L., Isolation and structure of combretastatin D-1: a cell growth inhibitory macrocyclic lactone from Combretum caffrum, J. Am. Chem. Soc., 110, 8539, 1988.
54. Singh, S.B. and Pettit, G.R., Antineoplastic agents. 206. Structure of the cytostatic macrocyclic lactone combretastatin D-2, J. Org. Chem., 55, 2797, 1990.
55. White, A., Principles of Biochemistry, 59th ed., McGraw-Hill, New York, 1978.
56. Nogales, E., Wolf, S.G., and Downing, K.H., Structure of the α,β-tubulin dimer by electron crystallography, Nature, 391, 199, 1998.
57. Rao, S., Horwitz, S.B., and Ringel, I., Direct photoaffinity labeling of tubulin with taxol, J. Natl. Cancer Inst., 84, 785, 1992.
58. Staretz, M.E. and Hastie, S.B., Synthesis, photochemical reactions, and tubulin binding of novel photoaffinity labeling derivatives of colchicine, J. Org. Chem., 58, 1589, 1993.
59. Hahn, K.M., Hastie, S.B., and Sundberg, R.J., Synthesis and evaluation of 2-diazo-3,3,3-trifluopropanoyl derivatives of colchicine and podophyllotoxin as photoaffinity labels: reactivity, photochemistry, and tubulin binding, Photochem. Photobiol., 55, 17, 1992.
60. Wolff, J. et al., Direct photoaffinity labeling of tubulin with colchicine, Proc. Natl. Acad. Sci. USA, 88, 2820, 1991.
61. Floyd, L.J., Barnes, L.D., and Williams, R.F., Photoaffinity labeling of tubulin with (2-nitro-4-azidophenyl)deacetylcolchicine: direct evidence for two colchicine binding sites, Biochemistry, 28, 8515, 1989.
62. Bai, R. et al., Identification of cysteine 354 of beta-tubulin as part of the binding site for the A ring of colchicine, J. Biol. Chem., 271, 12639, 1996.
63. Olszewski, J. D. et al., Potential photoaffinity labels for tubulin. Synthesis and evaluation of diazocyclohexadienone and azide analogs of colchicine, combretastatin, and 3,4,5-trimethoxybiphenyl, J. Org. Chem., 59, 4285, 1994.
64. Pinney, K.G. et al., Synthesis and biological evaluation of aryl azide derivatives of combretastatin A-4 as molecular probes for tubulin, Bioorg. Med. Chem., 8, 2417, 2000.
65. Sawada, T. et al., A fluorescent probe and a photoaffinity labeling reagent to study the binding site of maytansine and rhizoxin on tubulin, Bioconj. Chem., 4, 284, 1993.
66. Sawada, T. et al., Identification of the fragment photoaffinity-labeled with azidodansyl-rhizoxin as Met-363-Lys-379 on beta-tubulin, Biochem. Pharm., 45, 1387, 1993.
67. Sawada, T. et al., Fluorescent and photoaffinity labeling derivatives of rhizoxin, Biochem. Biophys. Res. Comm., 178, 558, 1991.
68. Chavan, A.J. et al., Forskolin photoaffinity probes for the evaluation of tubulin binding sites, Bioconj. Chem., 4, 268, 1993.
69. Safa, A.R., Hamel, E., and Felsted, R.L., Photoaffinity labeling of tubulin subunits with a photoactive analogue of vinblastine, Biochemistry, 26, 97, 1987.
70. Williams, R.F. et al., A photoaffinity derivative of colchicine: 6-(4-azido-2-nitrophenylamino)hexanoyldeacetylcolchicine; photolabeling and location of the colchicine-binding site on the alpha-subunit of tubulin, J. Biol. Chem., 260, 13794, 1985.
71. Nogales, E., Structural insights into microtubule function, Ann. Rev. Biochem., 69, 277, 2000.
72. Hadimani, M. et al., 2-(3-tert-Butyldimethylsiloxy-4-methoxyphenyl)-6-methoxy-3-(3,4,5-trimethoxybenzoyl) indole, Acta Cryst., Sec. C Crystal Struct. Comm., C58, 330, 2002.
73. Siemann, D.W., Vascular targeting agents: an introduction, Int. J. Radiat. Oncol. Biol. Phys., 54, 1472, 2002.
74. Chaplin, D.J. and Hill, S.A., The development of combretastatin A4 phosphate as a vascular targeting agent, Int. J. Radiat. Oncol. Biol. Phys., 54, 1491, 2002.
75. Thorpe, P.E., Chaplin, D.J., and Blakeley, D.C., The first international conference on vascular targeting: meeting overview, Cancer Res., 63, 1144, 2003.
76. Chaplin, D.J. and Dougherty, G.J., Tumour vasculature as a target for cancer therapy, Br. J. Cancer, 80, 57, 1999.
77. Kanthou, C. and Tozer, G.M., The tumor vascular targeting agent combretastatin A-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells, Blood, 99, 2060, 2002.
78. Tozer, G.M. et al., Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability, Cancer Res., 61, 6413, 2001.
79. Galbraith, S.M. et al., Effects of combretastatin A4 phosphate on endothelial cell morphology in vitro and relationship to tumor vascular targeting activity in vivo, Anticancer Res., 21, 93, 2001.
80. Young, S. and Chaplin, D.J., Combretastin A4 phosphate: background and current clinical status, Expert Opin. Investig. Drugs, 13, 1171, 2004.
81. Pettit, G.R. et al., Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4, Experientia, 45, 209, 1989.
82. Pettit, G.R. and Rhodes, M.R., Antineoplastic agents 389. New syntheses of the combretastatin A-4 prodrug, Anticancer Drug Des., 13, 183, 1998.
83. Boger, D.L., Sakya, S.M., and Yohannes, D., Total synthesis of combretastatin D-2: intramolecular Ullmann macrocyclization reaction, J. Org. Chem., 56, 4204, 1991.
84. Deleted from text.
85. Gaukroger, K. et al., Novel syntheses of cis and trans isomers of combretastatin A-4, J. Org. Chem., 66, 8135, 2001.
86. Bui, V.P. et al., Direct biooxidation of arenes to corresponding catechols with E. coli JM109 (PDTG602). Application to synthesis of combretastatins A-1 and B-1, Tetrahedron Lett., 43, 2839, 2002.
87. Lawrence, N.J. et al., The synthesis of (E) and (Z)-combretastatins A-4 and a phenanthrene from Combretum caffrum, Synthesis, 9, 1656, 1999.
88. Deshpande, V.H. and Gokhale, N.J., Synthesis of combretastatin D-2, Tetrahedron Lett., 33, 4213, 1992.
89. Couladouros, E.A. and Soufli, I.C., Total synthesis of natural (-)-combretastatin D-1, Tetrahedron Lett., 36, 9369, 1995.
90. Couladouros, E.A. and Soufli, I.C., Synthesis of combretastatin D-2. An efficient route to caffrane macrolactones, Tetrahedron Lett., 35, 4409, 1994.
91. Chaplin, D.J. et al., Functionalized stilbene derivatives as improved vascular targeting agents, US Patent 20030149003 A1, 2003.
92. Ohsumi, K. et al., Novel combretastatin analogues effective against murine solid tumors: design and structure-activity relationships, J. Med. Chem., 41, 3022, 1998.
93. Ohsumi, K. et al., Synthesis and antitumor activities of amino acid prodrugs of amino-combretastatins, Anticancer Drug Des., 14, 539, 1999.
94. Siles, R., Hadimani, M., and Pinney, K.G., Cancer chemotherapy: prodrug strategies for enhanced bioavailability and selectivity of vascular targeting agents, 58th Southwest Regional Meeting of The American Chemical Society (abstract 236), Austin, TX, November 4, 2002.
95. Pettit, G.R. et al., Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4-dimethoxy-3-amino-Z -stilbene and derived amino acid amides, J. Med. Chem., 46, 525, 2003.
96. Lawrence, N.J. et al., Synthesis and anticancer activity of fluorinated analogues of combretastatin A-4, J. Fluorine Chem., 123, 101, 2003.
97. Davis, P.D., Compositions with vascular damaging activity, PCT Int. Application WO0214329 A1, 2002.
98. Gaukroger, K., Structural requirements for the interaction of combretastatins with tubulin: how important is the trimethoxy unit? Org. Biomol. Chem., 1, 3033, 2003.
99. Pettit, G.R. et al., Antineoplastic agents. 379. Synthesis of phenstatin phosphate, J. Med. Chem., 41, 1688, 1998.
100. Pettit, G.R. et al., Antineoplastic agents. 443. Synthesis of the cancer cell growth inhibitor hydroxyphenstatin and its sodium diphosphate prodrug, J. Med. Chem., 43, 2731, 2000.
101. Medarde, M. et al., Synthesis and antineoplastic activity of combretastatin analogues: heterocombretastatins, European J. Med. Chem., 33, 71, 1998.
102. Andres, C.J. et al., “Combretatropones” — hybrids of combretastatin and colchicine. Synthesis and biochemical evaluation, Bioorg. Med. Chem. Lett., 3, 565, 1993.
103. Janik, M.E. and Bane, S.L., Synthesis and antimicrotubule activity of combretatropone derivatives, Bioorg. Med. Chem., 10, 1895, 2002.
104. Shirai, R. et al., Synthesis and anti-tubulin activity of aza -combretastatins, Bioorg. Med. Chem. Lett., 4, 699, 1994.
105. Pettit, G.R. et al., Antineoplastic agents. 410. Asymmetric hydroxylation of trans-combretastatin A-4, J. Med. Chem., 42, 1459, 1999.
106. Pettit, G.R. et al., Antineoplastic agents 440. Asymmetric synthesis and evaluation of the combretastatin A-1 SAR probes (1S, 2S)-and (1R, 2R)-1,2-dihydroxy-1-(2,3-dihydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-ethane, J. Nat. Prod., 63, 969, 2000.
107. Shirai, R. et al., Asymmetric synthesis of antimitotic combretadioxolane with potent antitumor activity against multi-drug resistant cells, Bioorg. Med. Chem. Lett., 8, 1997, 1998.
108. Pettit, G.R. et al., Antineoplastic agents 442. Synthesis and biological activities of dioxostatin, Anticancer Drug Des., 15, 361, 2000.
109. Shirai, R., Okabe, T., and Iwasaki, S., Synthesis of comformationally restricted combretastatins, Heterocycles, 46, 145, 1997.
110. Ducki, S. et al., Potent antimitotic and cell growth inhibitory properties of substituted chalcones, Bioorg. Med. Chem. Lett., 8, 1051, 1998.
111. Wang, L. et al., Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation, J. Med. Chem ., 45, 1697, 2002.
112. Hatanaka, T. et al., Novel B ring modified combretastatin analogues: syntheses and antineoplastic activity, Bioorg. Med. Chem. Lett., 8, 3371, 1998.
113. Medina, J.C. et al., Pentafluorobenzenesulfonamides and analogs, US Patent 5880151, 1999.
114. Flygare, J.A. et al., Pentafluorobenzenesulfonamides and analogs, US Patent 6121304, 2000.
115. Pinney, K.G., Wang, F., and Del Pilar Mejia, M., Preparation of indole-containing and combretastatinrelated anti-mitotic and anti-tubulin polymerization agents, PCT Int. Application WO2001019794 A2, 2001.
116. Flynn, B.L., Hamel, E., and Jung, M.K., One-pot synthesis of benzo[b]furan and indole inhibitors of tubulin polymerization, J. Med. Chem., 45, 2670, 2002.
117. Gastpar, R. et al., Methoxy-substituted 3-formyl-2-phenylindoles inhibit tubulin polymerization, J. Med. Chem., 41, 4965, 1998.
118. Chen, Z. et al., Preparation of new anti-tubulin ligands through a dual-mode, addition-elimination reaction to a bromo-substituted,-unsaturated sulfoxide, J. Org. Chem., 65, 8811, 2000.
119. Pinney, K.G. et al., Preparation of trimethoxyphenyl-containing tubulin binding ligands and corresponding prodrug constructs as inhibitors of tubulin polymerization and antimitotic agents, PCT Int. Application WO2001068654, 2001.
120. Pinney, K.G. et al., Anti-mitotic agents which inhibit tubulin polymerization, US Patent 6162930, 2000.
121. Pinney, K.G. et al., Anti-mitotic agents which inhibit tubulin polymerization, Australian Patent 732917, 2001.
122. Flynn, B.L. et al., The synthesis and tubulin binding activity of thiophene-based analogues of combretastatin A-4, Bioorg. Med. Chem. Lett., 11, 2341, 2001.
123. Flynn, B.L., Verdier-Pinard, P., and Hamel, E., A novel palladium-mediated coupling approach to 2,3-disubstituted benzo[b]thiophenes and its application to the synthesis of tubulin binding agents, Org. Lett., 3, 651, 2001.
124. Pinney, K.G. et al., Preparation of aryl and arylcarbonylbenzothiophenes, -benzofurans, -indenes, and indoles as tubulin binding ligands and corresponding prodrug constructs thereof useful as antitumor agents, US Patent 2004044059, 2004.
125. Flynn, B.L. and Hamel, E., Synthesis of indoles, benzofurans, and related compounds as potential tubulin binding agents, PCT Int. Application WO2002060872 A1, 2002.
126. Pinney, K.G. et al., Tubulin binding ligands and corresponding prodrug constructs, US Patent 6593374, 2003.
127. Ghatak, A. et al., Synthesis of methoxy and hydroxy containing tetralones: versatile intermediates for the preparation of biologically relevant molecules, Tetrahedron Lett., 44, 4145, 2003.
128. Goldbrunner, M. et al., Inhibition of tubulin polymerization by 5,6-dihydroindolo[2,1-α ]isoquinoline derivatives, J. Med. Chem., 40, 3524, 1997.
129. Li, Q. et al., Synthesis and biological evaluation of 2-indolyloxazolines as a new class of tubulin polymerization inhibitors. Discovery of A-289099 as an orally active antitumor agent, Bioorg. Med. Chem. Lett., 12, 465, 2002.
130. Tahir, S.K. et al., Biological activity of A-289099: an orally active tubulin-binding indolyloxazoline derivative, Mol. Cancer Ther., 2, 227, 2003.
131. Hori, K. and Saito, S., Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis, Br. J. Cancer, 89, 1334, 2003.
132. Blakey, D.C. et al., ZD6126: a novel small molecule vascular targeting agent, Int. J. Radiat. Onc. Biol. Phys., 54, 1497, 2002.
133. Siemann, D.W. and Rojiani, A.M., Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126, Int. J. Radiat. Oncol. Biol. Phys., 54, 1512, 2002.
134. Siemann, D.W. and Rojiani, A.M., Enhancement of radiation therapy by the novel vascular targeting agent ZD6126, Int. J. Radiat. Oncol. Biol. Phys., 53, 164, 2002.
135. Micheletti, G. et al., Vascular-targeting activity of ZD6126, a novel tubulin-binding agent, Cancer Res., 63, 1534, 2003.
136. Chaplin, D.J. et al., Antivascular approaches to solid tumour therapy: evaluation of tubulin binding agents, Br. J. Cancer, 27, S86, 1996.
137. Dark, G.D. et al., Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature, Cancer Res., 57, 1829, 1997.
138. West, C.M.L. and Price, P., Combretastatin A4 phosphate, Anticancer Drugs, 15, 179, 2004.
139. McGown, A.T. and Fox, B.W., Structural and biochemical comparison of the anti-mitotic agents colchicine, combretastatin A4 and amphethinile, Anticancer Drug Des., 3, 249, 1989.
140. Hamel, E. and Lin, C.M., Interactions of combretastatin, a new plant-derived antimitotic agent, with tubulin, Biochem. Pharm., 32, 3864, 1983.
141. Horsman, M.R. et al., The effect of combretastatin A-4 disodium phosphate in a C3H mouse mammary carcinoma and a variety of murine spontaneous tumors, Int. J. Radiat. Oncol. Biol. Phys., 42, 895, 1998.
142. Li, L., Rojiani, A., and Siemann, D.W., Targeting the tumor vasculature with combretastatin A-4 disodium phosphate: effects on radiation therapy, Int. J. Radiat. Oncol. Biol. Phys., 42, 899, 1998.
143. Tozer, G.M., et al., Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues, Cancer Res., 57, 1829, 1997.
144. Grosios, K. et al., In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug, Br. J. Cancer, 81, 1318, 1999.
145. Beauregard, D.A. et al., Magnetic resonance imaging and spectroscopy of combretastatin A4 prodruginduced disruption of tumour perfusion and energetic status, Br. J. Cancer, 77, 1761, 1998.
146. Eikesdal, H.P. et al., The new tubulin-inhibitor combretastatin A-4 enhances thermal damage in the BT4An rat glioma, Int. J. Radiat. Oncol. Biol. Phys., 46, 645, 2000.
147. Maxwell, R.J. et al., Effects of combretastatin on murine tumours monitored by 31 P MRS, 1 H MRS and 1 H MRI, Int. J. Radiat. Oncol. Biol. Phys., 42, 891, 1998.
148. Ahmed, B. et al., Vascular targeting effect of combretastatin A-4 phosphate dominates the inherent angiogenesis inhibitory activity, Int. J. Cancer, 105, 20, 2003.
149. Chaplin, D.J. and Horsman, M.R., The influence of tumour temperature on ischemia-induced cell death: potential implications for the evaluation of vascular mediated therapies, Radiother. Oncol., 30, 59, 1994.
150. Siemann, D.W. et al., Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy, Int. J. Cancer, 99, 1, 2002.
151. Chaplin, D.J. et al., Therapeutic significance of microenvironmental factors, Medical Radiology, (Radiation Oncology): Blood Perfusion and Microenvironment of Human Tumors, Springer, Berlin, 1998, 133.
152. Horsman, M.R. et al., Combretastatins: novel vascular targeting drugs for improving anti-cancer therapy. Combretastatins and conventional therapy, Adv. Exp. Med. Biol., 476, 311, 2000.
153. Landuyt, W. et al., In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment, Int. J. Radiat. Oncol. Biol. Phys., 49, 443, 2001.
154. Horsman, M.R. and Murata, R., Combination of vascular targeting agents with thermal or radiation therapy, Int. J. Radiation Oncol. Biol. Phys., 54, 1518, 2002.
155. Pedley, R.B. et al., Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin A-4 3-O-phosphate, Cancer Res., 61, 4716, 2001.
156. Grosios, K. et al., Combination chemotherapy with combretastatin A-4 phosphate and 5-fluorouracil in an experimental murine colon adenocarcinoma, Anticancer Res., 20, 229, 2000.
157. Nelkin, B.D. and Ball, D.W., Combretastatin A-4 and doxorubicin combination treatment is effective in a preclinical model of human medullary thyroid carcinoma, Oncol. Rep., 8, 157, 2001.
158. Wildiers, H. et al., Combretastatin A-4 phosphate enhances CPT-11 activity independently of the administration sequence, Eur. J. Cancer, 40, 284, 2004.
159. Murata, R. et al., Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumors, Radiother. Oncol., 60, 155, 2001.
160. Murata, R., Overgaard, J., and Horsman, M.R., Combretastatin A-4 disodium phosphate: a vascular targeting agent that improves that improves the anti-tumor effects of hyperthermia, radiation, and mild thermoradiotherapy, Int. J. Radiat. Oncol. Biol. Phys., 51, 1018, 2001.
161. Horsman, M.R., Christensen, K.L., and Overgaard, J., Hydralazine-induced enhancement of hyperthermic damage in a C3H mammary carcinoma in vivo, Int. J. Hyperthermia, 5, 123, 1989.
162. Eikesdal, H.P. et al., Combretastatin A-4 and hyperthermia; a potent combination for the treatment of solid tumors, Radiother. Oncol., 60, 147, 2001.
163. Holwell, S.E. et al., Anti-tumor and anti-vascular effects of the novel tubulin-binding agent combretastatin A-1 phosphate, Anticancer Res., 22, 3933, 2002.
164. Hill, S.A. et al., Preclinical evaluation of the antitumour activity of the novel vascular targeting agent OXi 4503, Anticancer Res., 22, 1453, 2002.
165. Shnyder, S.D. et al., Combretastatin A-1 phosphate potentiates the antitumour activity of cisplatin in a murine adenocarcinoma model, Anticancer Res., 23, 1619, 2003.
166. Hua, J. et al., Oxi4503, a novel vascular targeting agent: effects on blood flow and antitumor activity in comparison to combretastatin A-4 phosphate, Anticancer Res., 23, 1433, 2003.
167. Kirwan, I.G. et al., Comparative preclinical pharmacokinetic and metabolic studies of the combretastatin prodrugs combretastatin A4 phosphate and A1 phosphate, Clin. Cancer Res., 10, 1446, 2004.
168. Dowlati, A. et al., A phase 1b pharmacokinetic and translational study of the novel vascular targeting agent combretastatin A-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer, Cancer Res., 62, 3408, 2002.
169. Stevenson, J.P. et al., Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow, J. Clin. Oncol., 21, 4428, 2003.
170. Rustin, G.J. et al., Phase I clinical trial of weekly combretastatin A4 phosphate: clinical and pharmacokinetic results, J. Clin. Oncol., 21, 2815, 2003.
171. Galbraith, S.M. et al., Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging, J. Clin. Oncol., 21, 2831, 2003.
172. Anderson, H.L. et al., Assessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate, J. Clin. Oncol., 21, 2823, 2003.