Tubulin colchicine binding site inhibitors as vascular disrupting agents in clinical developments

Current Medicinal Chemistry

Volumn 22, Issue 11, 2015, Pages 1348-1360

  Ji, Ya Ting ^a   Liu, Yan Na ^a   Liu, Zhao Peng ^a  

^a SHANDONG UNIVERSITY   (China)

Author keywords

Anticancer; Antitumor; Antivascular; Clinical trials; Colchicine binding site; Tubulin inhibitors; Vascular disrupting agents (VDAs)

Indexed keywords

6 METHOXY 2 METHYL 3 (3,4,5 TRIMETHOXYBENZOYL)BENZOFURAN 7 YL PHOSPHATE DISODIUM; BNC 105; CKD 516; COLCHICINE; COMBRETASTATIN A1 PHOSPHATE; COMBRETASTATIN A4; COMBRETASTATIN A4 PHOSPHATE; CROLIBULIN; DENIBULIN; LEXIBULIN; N ACETYLCOLCHINOL PHOSPHATE; N [2 [(4 HYDROXYPHENYL)AMINO] 3 PYRIDINYL] 4 METHOXYBENZENESULFONAMIDE; OMBRABULIN; PLINABULIN; TUBULIN; UNCLASSIFIED DRUG; VASCULAR TARGETING AGENT; VERUBULIN; ANTINEOPLASTIC AGENT; TUBULIN MODULATOR;

APOPTOSIS; CLINICAL TRIAL (TOPIC); DEPOLYMERIZATION; DRUG BINDING SITE; ENDOTHELIUM CELL; HUMAN; IC50; IN VITRO STUDY; IN VIVO STUDY; MICROTUBULE; MICROTUBULE ASSEMBLY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; TUMOR BLOOD FLOW; TUMOR VASCULARIZATION; VASCULAR TUMOR; VOLUME OF DISTRIBUTION AT STEADY-STATE; BINDING SITE; CHEMISTRY; DRUG EFFECTS; METABOLISM; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC;

ANTINEOPLASTIC AGENTS; BINDING SITES; COLCHICINE; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; TUBULIN; TUBULIN MODULATORS;

EID: 84924956325     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867322666150114163732     Document Type: Review

References (79)

1. Carmeliet, P.; Jain, R.K. Molecular mechanisms and clinical applications of angiogenesis. Nature, 2011, 473 (7347), 298-307.
2. Baguley, B.C. Preclinical efficacy of vascular disrupting agents in non-small-cell lung cancer. Clin. Lung Cancer, 2011, 12(2), 81-86.
3. Cai, S.X. Small molecule vascular disrupting agents: potential new drugs for cancer treatment. Recent Pat. Anti-Cancer Drug Discovery, 2007, 2, 79-101.
4. von, P.J.; Gorbounova, V.; Reck, M.; Kowalski, D.M.; Allard, A.; Chadjaa, M.; Rey, A.; Bennouna, J.; Grossi, F. Disrupt: a randomised phase 2 trial of ombrabulin (AVE8062) plus a taxane-platinum regimen as first-line therapy for metastatic non-small cell lung cancer. Lung Cancer, 2014.
5. Hasani, A.; Leighl, N. Classification and toxicities of vascular disrupting agents. Clin. Lung Cancer, 2011, 12(1), 18-25.
6. Vincent, L.; Kermani, P.; Young, L.M.; Cheng, J.; Zhang, F.; Shido, K.; Lam, G.; Bompais-Vincent, H.; Zhu, Z.; Hicklin, D.J.; Bohlen, P.; Chaplin, D.J.; May, C.; Rafii, S. Combretastatin A4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling. J. Clin. Invest., 2005, 115(11), 2992-3006.
7. Monk, K.A.; Siles, R.; Hadimani, M.B.; Mugabe, B.E.; Ackley, J.F.; Studerus, S.W.; Edvardsen, K.; Trawick, M.L.; Garner, C.M.; Rhodes, M.R.; Pettit, G.R.; Pinney, K.G. Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents. Bioorg. Med. Chem., 2006, 14, 3231-3244.
8. Kretzschmann, V.K.; Fuerst, R. Plant-derived vascular disrupting agents: compounds, actions, and clinical trials. Phytochem. Rev., 2014, 13, 191-206.
9. Nicholson, B.; Lloyd, G.K.; Miller, B.R.; Palladino, M.A.; Kiso, Y.; Hayashi, Y.; Neuteboom, S.T.C. NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent. Anticancer Drugs, 2006, 17, 25-31.
10. Pilat, M.J.; Lorusso, P.M. Vascular disrupting agents. J. Cell. Biochem., 2006, 99 (4), 1021-1039.
11. Kanthou, C.; Tozer, G.M. Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int. J. Exp. Pathol., 2009, 90, 284-294.
12. Subbiah, I.M.; Lenihan, D.J.; Tsimberidou, A.M. Cardiovascular toxicity profiles of vascular-disrupting agents. Oncologist, 2011, 16 (8), 1120-1130.
13. Lin, C.M.; Singh, S.B.; Chu, P.S.; Dempcy, R.O.; Schmidt, J.M.; Pettit, G.R.; Hamel, E. Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study. Mol. Pharmacol., 1988, 34(2), 200-208.
14. Massarotti, A.; Coluccia, A.; Silvestri, R.; Sorba, G.; Brancale, A. The tubulin colchicine domain: a molecular modeling perspective. ChemMedChem., 2012, 7 (1), 33-42.
15. Srivastava, V.; Negi, A.S.; Kumar, J.K.; Gupta, M.M.; Khanuja, S.P.S. Plant-based anticancer molecules: A chemical and biological profile of some important leads. Bioorg. Med. Chem., 2005, 13(21), 5892-5908.
16. Shan, Y.; Zhang, J.; Liu, Z.; Wang, M.; Dong, Y. Developments of combretastatin A-4 derivatives as anticancer agents. Curr. Med. Chem., 2011, 18(4), 523-538.
17. Young, S.L.; Chaplin, D.J. Combretastatin A4 phosphate: background and current clinical status. Expert Opin. Investig. Drugs, 2004, 13(9), 1171-1182.
18. Kanthou, C.; 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, 2002, 99 (6), 2060-2069.
19. Mooney, C.J.; Nagaiah, G.; Fu, P.; Wasman, J.K.; Cooney, M.M.; Savvides, P.S.; Bokar, J.A.; Dowlati, A.; Wang, D.; Agarwala, S.S.; Flick, S.M.; Hartman, P.H.; Ortiz, J.D.; Lavertu, P.N.; Remick, S.C. A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid, 2009, 19(3), 233-240.
20. Lee, R.M.; Gewirtz, D.A. Colchicine site inhibitors of microtubule integrity as vascular disrupting agents. Drug Dev. Res., 2008, 69, 352-358.
21. Salmon, H.W. Effect of the second-generation vascular disrupting agent OXi4503 on tumor vascularity. Clin. Cancer Res., 2006, 12(13), 4090-4094.
22. Cummings, J.; Zweifel, M.; Smith, N.; Ross, P.; Peters, J.; Rustin, G.; Price, P.; Middleton, M.R.; Ward, T.; Dive, C. Evaluation of cell death mechanisms induced by the vascular disrupting agent OXi4503 during a phase I clinical trial. Br. J. Cancer, 2012, 106(11), 1766-1771.
23. Patterson, D.M.; Zweifel, M.; Middleton, M.R.; Price, P.M.; Folkes, L.K.; Stratford, M.R.; Ross, P.; Halford, S.; Peters, J.; Balkissoon, J.; Chaplin, D.J.; Padhani, A.R.; Rustin, G.J. Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors. Clin. Cancer Res., 2012, 18(5), 1415-1425.
24. Hori, K.; Saito, S. Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis. Br. J. Cancer, 2003, 89(7), 1334-1344.
25. Sessa, C.; Lorusso, P.; Tolcher, A.; Farace, F.; Lassau, N.; Delmonte, A.; Braghetti, A.; Bahleda, R.; Cohen, P.; Hospitel, M.; Veyrat-Follet, C.; Soria, J.-C. Phase I safety, pharmacokinetic and pharmacodynamic evaluation of the vascular disrupting agent ombrabulin (AVE8062) in patients with advanced solid tumors. Clin. Cancer Res., 2013, 19, 4832-4842.
26. Clemenson, C.; Jouannot, E.; Merino-Trigo, A.; Rubin-Carrez, C.; Deutsch, E. The vascular disrupting agent ombrabulin (AVE8062) enhances the efficacy of standard therapies in head and neck squamous cell carcinoma xenograft models. Invest. New Drugs, 2013, 31(2), 273-284.
27. Lee, J.; Bae, S.; Lee, S.H.; Choi, H.; Kim, Y.H.; Kim, S.J.; Park, G.T.; Moon, S.K.; Kim, D.H.; Lee, S.; Ahn, S.K.; Choi, N.S.; Lee, K.J. Discovery of a potent tubulin polymerization inhibitor: synthesis and evaluation of water-soluble prodrugs of benzophenone analog. Bioorg. Med. Chem. Lett., 2010, 20(21), 6327-6330.
28. Lee, J.; Kim, S.J.; Choi, H.; Kim, Y.H.; Lim, I.T.; Yang, H.-m.; Lee, C.S.; Kang, H.R.; Ahn, S.K.; Moon, S.K.; Kim, D.-H.; Lee, S.; Choi, N.S.; Lee, K.J. Identification of CKD-516: a potent tubulin polymerization inhibitor with marked antitumor activity against murine and human solid tumors. J. Med. Chem., 2010, 53, 6337-6354.
29. Kim, K.W.; Lee, J.M.; Jeon, Y.S.; Lee, I.J.; Choi, Y.S.; Park, J.; Kiefer, B.; Kim, C.; Han, J.K.; Choi, B.I. Vascular disrupting effect of CKD-516: preclinical study using DCE-MRI. Invest. New Drugs, 2013, 31, 1097-1106.
30. Kremmidiotis, G.; Leske, A.F.; Lavranos, T.C.; Beaumont, D.; Gasic, J.; Hall, A.; O'Callaghan, M.; Matthews, C.A.; Flynn, B. BNC105: a novel tubulin polymerization inhibitor that selectively disrupts tumor vasculature and displays single-agent antitumor efficacy. Mol. Cancer Ther., 2010, 9, 1562-1573.
31. Rischin, D.; Bibby, D.C.; Chong, G.; Kremmidiotis, G.; Leske, A.F.; Matthews, C.A.; Wong, S.S.; Rosen, M.A.; Desai, J. Clinical, pharmacodynamic, and pharmacokinetic evaluation of BNC105P: a phase I trial of a novel vascular disrupting agent and inhibitor of cancer cell proliferation. Clin. Cancer Res., 2011, 17(15), 5152-5160.
32. Nowak, A.K.; Brown, C.; Millward, M.J.; Creaney, J.; Byrne, M.J.; Hughes, B.; Kremmidiotis, G.; Bibby, D.C.; Leske, A.F.; Mitchell, P.L.; Pavlakis, N.; Boyer, M.; Stockler, M.R. A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma. Lung Cancer, 2013, 81(3), 422-427.
33. Cao, T.M.; Durrant, D.; Tripathi, A.; Liu, J.; Tsai, S.; Kellogg, G.E.; Simoni, D.; Lee, R.M. Stilbene derivatives that are colchicine-site microtubule inhibitors have antileukemic activity and minimal systemic toxicity. Am. J. Hematol., 2008, 83 (5), 390-397.
34. Durrant, D.; Corwin, F.; Simoni, D.; Zhao, M.; Rudek, M.A.; Salloum, F.N.; Kukreja, R.C.; Fatouros, P.P.; Lee, R.M. cis-3, 4′, 5-Trimethoxy-3′-aminostilbene disrupts tumor vascular perfusion without damaging normal organ perfusion. Cancer Chemother. Pharmacol., 2009, 63(2), 191-200.
35. Durrant, D.E.; Richards, J.; Tripathi, A.; Kellogg, G.E.; Marchetti, P.; Eleopra, M.; Grisolia, G.; Simoni, D.; Lee, R.M. Development of water soluble derivatives of cis-3, 4′, 5-trimethoxy-3′-aminostilbene for optimization and use in cancer therapy. Invest. New Drugs, 2009, 27, 41-52.
36. Kuo, C.C.; Hsieh, H.P.; Pan, W.Y.; Chen, C.P.; Liou, J.P.; Lee, S.J.; Chang, Y.L.; Chen, L.T.; Chen, C.T.; Chang, J.Y. BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res., 2004, 64(13), 4621-4628
37. Chen, C.P.; Hu, C.B.; Yeh, K.C.; Song, J.S.; Yeh, T.K.; Tung, F.F.; Hwang, L.L.; Tseng, H.Y.; Huang, Y.C.; Shy, H.S.; Hsieh, S.H.; Shen, C.C.; Wang, H.S.; Hsieh, H.P.; Liou, J.P.; Chao, Y.S.; Chen, C.T. Antiangiogenic activities and cisplatin-combined antitumor activities of BPR0L075. Anticancer Res., 2010, 30(7), 2813-2822.
38. Liu, L.; Beck, H.; Wang, X.; Hsieh, H.-P.; Mason, R.P.; Liu, X. Tubulin-destabilizing agent BPR0L075 induces vascular-disruption in human breast cancer mammary fat pad xenografts. PLoS One, 2012, 7, e43314.
39. Zaninetti, R.; Cortese, S.V.; Aprile, S.; Massarotti, A.; Canonico, P.L.; Sorba, G.; Grosa, G.; Genazzani, A.A.; Pirali, T. A concise synthesis of pyrazole analogs of combretastatin A1 as potent antitubulin agents. ChemMedChem, 2013, 8, 633-643.
40. Kentaro Yoshimatsu, A.Y.; Hiroshi Yoshino; Nozomu Koyanagi; Kyosuke Kitoh. Mechanism of action of E7010, an orally active sulfonamide antitumor agent: inhibition of mitosis by binding to the colchicine site of tubulin. Cancer Res., 1997, 57, 3208-3213.
41. Yee, K.W.L.; Hagey, A.; Verstovsek, S.; Cortes, J.; Garcia-Manero, G.; O'Brien, S.M.; Faderl, S.; Thomas, D.; Wierda, W.; Kornblau, S.; Ferrajoli, A.; Albitar, M.; McKeegan, E.; Grimm, D.R.; Mueller, T.; Holley-Shanks, R.R.; Sahelijo, L.; Gordon, G.B.; Kantarjian, H.M.; Giles, F.J. Phase 1 study of ABT-751, a novel microtubule inhibitor, in patients with refractory hematologic malignancies. Clin. Cancer Res., 2005, 11, 6615-6624.
42. Segreti, J.A.; Polakowski, J.S.; Koch, K.A.; Marsh, K.C.; Bauch, J.L.; Rosenberg, S.H.; Sham, H.L.; Cox, B.F.; Reinhart, G.A. Tumor selective antivascular effects of the novel antimitotic compound ABT-751: an in vivo rat regional hemodynamic study. Cancer Chemother. Pharmacol., 2004, 54, 273-281.
43. Luo, Y.; Hradil, V.P.; Frost, D.J.; Rosenberg, S.H.; Gordon, G.B.; Morgan, S.J.; Gagne, G.D.; Cox, B.F.; Tahir, S.K.; Fox, G.B. ABT-751, a novel tubulin-binding agent, decreases tumor perfusion and disrupts tumor vasculature. Anti-Cancer Drugs, 2009, 20, 483-492.
44. Mauer, A.M.; Cohen, E.E.W.; Ma, P.C.; Kozloff, M.F.; Schwartzberg, L.; Coates, A.I.; Qian, J.; Hagey, A.E.; Gordon, G.B. A phase II study of ABT-751 in patients with advanced non-small cell lung cancer. J. Thorac. Oncol., 2008, 3, 631-636.
45. Hande, K.R.; Hagey, A.; Berlin, J.; Cai, Y.; Meek, K.; Kobayashi, H.; Lockhart, A.C.; Medina, D.; Sosman, J.; Gordon, G.B.; Rothenberg, M.L. The pharmacokinetics and safety of ABT-751, a novel, orally bioavailable sulfonamide antimitotic agent: results of a phase 1 study. Clin. Cancer Res., 2006, 12, 2834-2840.
46. Fox, E.; Maris, J.M.; Widemann, B.C.; Meek, K.; Goodwin, A.; Goodspeed, W.; Kromplewski, M.; Fouts, M.E.; Medina, D.; Cho, S.Y.; Cohn, S.L.; Krivoshik, A.; Hagey, A.E.; Adamson, P.C.; Balis, F.M. A Phase 1 Study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 7 days every 21 days in pediatric patients with solid tumors. Clin. Cancer Res., 2006, 12, 4882-4887.
47. Rudin, C.M.; Mauer, A.; Smakal, M.; Juergens, R.; Spelda, S.; Wertheim, M.; Coates, A.; McKeegan, E.; Ansell, P.; Zhou, X.; Qian, J.; Pradhan, R.; Dowell, B.; Krivoshik, A.; Gordon, G. Phase I/II study of pemetrexed with or without ABT-751 in advanced or metastatic non-small-cell lung cancer. J. Clin. Oncol., 2011, 29(8), 1075-1082.
48. Meany, H.J.; Sackett, D.L.; Maris, J.M.; Ward, Y.; Krivoshik, A.; Cohn, S.L.; Steinberg, S.M.; Balis, F.M.; Fox, E. Clinical outcome in children with recurrent neuroblastoma treated with ABT-751 and effect of ABT-751 on proliferation of neuroblastoma cell lines and on tubulin polymerization in vitro. Pediatr. Blood Cancer, 2010, 54, 47-54.
49. Fox, E.; Mosse, Y.P.; Meany, H.M.; Gurney, J.G.; Khanna, G.; Jackson, H.A.; Gordon, G.; Shusterman, S.; Park, J.R.; Cohn, S.L.; Adamson, P.C.; London, W.B.; Maris, J.M.; Balis, F.M. Time to disease progression in children with relapsed or refractory neuroblastoma treated with ABT-751: a report from the Children's Oncology Group (ANBL0621). Pediatr. Blood Cancer, 2014, 61, 990-996.
50. Lee, H.-Y.; Pan, S.-L.; Su, M.-C.; Liu, Y.-M.; Kuo, C.-C.; Chang, Y.-T.; Wu, J.-S.; Nien, C.-Y.; Mehndiratta, S.; Chang, C.-Y.; Wu, S.-Y.; Lai, M.-J.; Chang, J.-Y.; Liou, J.-P. Furanylazaindoles: potent anticancer agents in vitro and in vivo. J. Med. Chem., 2013, 56, 8008-8018.
51. Burns, C.J.; Harte, M.F.; Bu, X.; Fantino, E.; Joffe, M.; Sikanyika, H.; Su, S.; Tranberg, C.E.; Wilson, N.; Charman, S.A.; Shackleford, D.M.; Wilks, A.F. Discovery of CYT997: a structurally novel orally active microtubule targeting agent. Bioorg. Med. Chem. Lett., 2009, 19(16), 4639-4642.
52. Burns, C.J.; Fantino, E.; Powell, A.K.; Shnyder, S.D.; Cooper, P.A.; Nelson, S.; Christophi, C.; Malcontenti-Wilson, C.; Dubljevic, V.; Harte, M.F.; Joffe, M.; Phillips, I.D.; Segal, D.; Wilks, A.F.; Smith, G.D. The microtubule depolymerizing agent CYT997 causes extensive ablation of tumor vasculature in vivo. J. Pharmacol. Exp. Ther., 2011, 339(3), 799-806.
53. Lickliter, J.D.; Francesconi, A.B.; Smith, G.; Burge, M.; Coulthard, A.; Rose, S.; Griffin, M.; Milne, R.; McCarron, J.; Yeadon, T.; Wilks, A.; Cubitt, A.; Wyld, D.K.; Vasey, P.A. Phase I trial of CYT997, a novel cytotoxic and vascular-disrupting agent. Br. J. Cancer, 2010, 103(5), 597-606.
54. Monaghan, K.; Khong, T.; Smith, G.; Spencer, A. CYT997 causes apoptosis in human multiple myeloma. Invest. New Drugs, 2011, 29(2), 232-238.
55. Chen, X.; Yang, C.; Xu, Y.; Zhou, H.; Liu, H.; Qian, W. The microtubule depolymerizing agent CYT997 effectively kills acute myeloid leukemia cells via activation of caspases and inhibition of PI3K/Akt/mTOR pathway proteins. Exp. Ther. Med., 2013, 6(2), 299-304.
56. Yakushiji, F.; Tanaka, H.; Muguruma, K.; Iwahashi, T.; Yamazaki, Y.; Hayashi, Y. Water-soluble prodrug of antimicrotubule agent plinabulin: effective strategy with click chemistry. Chem. - Eur. J., 2011, 17(45), 12587-12590.
57. Mita, M.M.; Spear, M.A.; Yee, L.K.; Mita, A.C.; Heath, E.I.; Papadopoulos, K.P.; Federico, K.C.; Reich, S.D.; Romero, O.; Malburg, L.; Pilat, M.; Lloyd, G.K.; Neuteboom, S.T.; Cropp, G.; Ashton, E.; LoRusso, P.M. Phase 1 first-in-human trial of the vascular disrupting agent plinabulin (NPI-2358) in patients with solid tumors or lymphomas. Clin. Cancer Res., 2010, 16(23), 5892-5899.
58. Millward, M.; Mainwaring, P.; Mita, A.; Federico, K.; Lloyd, G.K.; Reddinger, N.; Nawrocki, S.; Mita, M.; Spear, M.A. Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel. Invest. New Drugs, 2012, 30, 1065-1073.
59. Micheletti, G.; Poli, M.; Borsotti, P.; Martinelli, M.; Imberti, B.; Taraboletti, G.; Giavazzi, R. Vascular-targeting activity of ZD6126, a novel tubulin-binding agent. Cancer Res., 2003, 63(7), 1534-1537.
60. Goto, H.; Yano, S.; Zhang, H.; Matsumori, Y.; Ogawa, H.; Blakey, D.C.; Sone, S. Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice. Cancer Res., 2002, 62(13), 3711-3715.
61. Goto, H.; Yano, S.; Matsumori, Y.; Ogawa, H.; Blakey, D.C.; Sone, S. Sensitization of tumor-associated endothelial cell apoptosis by the novel vascular-targeting agent ZD6126 in combination with cisplatin. Clin. Cancer Res., 2004, 10(22), 7671-7676.
62. Horner, S.A.; Gould, S.; Noakes, J.P.; Rattray, N.J.; Allen, S.L.; Zotova, E.; Arezzo, J.C. Lack of neurotoxicity of the vascular targeting agent ZD6126 following repeated i.v. dosing in the rat. Mol. Cancer Ther., 2004, 3(7), 783-791.
63. LoRusso, P.M.; Gadgeel, S.M.; Wozniak, A.; Barge, A.J.; Jones, H.K.; DelProposto, Z.S.; DeLuca, P.A.; Evelhoch, J.L.; Boerner, S.A.; Wheeler, C. Phase I clinical evaluation of ZD6126, a novel vascular-targeting agent, in patients with solid tumors. Invest. New Drugs, 2008, 26(2), 159-167.
64. Siemann, D.W.; Shi, W. Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors. Int. J. Radiat. Oncol., Biol., Phys., 2004, 60(4), 1233-1240.
65. Giavazzi, R.; Bani, M.R.; Taraboletti, G. Tumor-host interaction in the optimization of paclitaxel-based combination therapies with vascular targeting compounds. Cancer Metastasis Rev., 2007, 26, 481-488.
66. Shi, W.; Siemann, D.W. Preclinical studies of the novel vascular disrupting agent MN-029. Anticancer Res., 2005, 25, 3899-3904.
67. Ricart, A.D.; Ashton, E.A.; Cooney, M.M.; Sarantopoulos, J.; Brell, J.M.; Feldman, M.A.; Ruby, K.E.; Matsuda, K.; Munsey, M.S.; Medina, G.; Zambito, A.; Tolcher, A.W.; Remick, S.C. A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors. Cancer Chemother. Pharmacol., 2011, 68, 959-970.
68. Traynor, A.M.; Gordon, M.S.; Alberti, D.; Mendelson, D.S.; Munsey, M.S.; Wilding, G.; Gammans, R.E.; Read, W.L. A dose escalation, safety, and tolerability study of MN-029 in patients with advanced solid tumors. Invest. New Drugs, 2010, 28, 509-515.
69. Kasibhatla, S.; Baichwal, V.; Cai, S.X.; Roth, B.; Skvortsova, I.; Skvortsov, S.; Lukas, P.; English, N.M.; Sirisoma, N.; Drewe, J.; Pervin, A.; Tseng, B.; Carlson, R.O.; Pleiman, C.M. MPC-6827: A small-molecule inhibitor of microtubule formation that is not a substrate for multidrug resistance pumps. Cancer Res., 2007, 67, 5865-5871.
70. Grossmann, K.F.; Colman, H.; Akerley, W.A.; Glantz, M.; Matsuoko, Y.; Beelen, A.P.; Yu, M.; Groot, J.F.; Aiken, R.D.; Olsen, J.J.; Evans, B.A.; Jensen, R.L. Phase I trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme. J. Neuro-Oncol., 2012, 110, 257-264.
71. Pleiman, C.; Valppu, L.; Bhoite L.; Austin, H.; Taylor, J.; Baichwal, V.; Laughlin, M.; Carlson, R. Vascular disruption effects of MPC-6827, 98th AACR Annual Meeting, Los Angeles, CA, US, April 14-18, 2007.
72. Tsimberidou, A.-M.; Akerley, W.; Schabel, M.C.; Hong, D.S.; Uehara, C.; Chhabra, A.; Warren, T.; Mather, G.G.; Evans, B.A.; Woodland, D.P.; Swabb, E.A.; Kurzrock, R. Phase I clinical trial of MPC-6827 (Azixa), a microtubule destabilizing agent, in patients with advanced cancer. Mol. Cancer Ther., 2010, 9, 3410-3419.
73. Mahal, K.; Resch, M.; Ficner, R.; Schobert, R.; Biersack, B.; Mueller, T. Effects of the tumor-vasculature-disrupting agent verubulin and two heteroaryl analogues on cancer cells, endothelial cells, and blood vessels. ChemMedChem, 2014, 9, 847-854.
74. Thomas, P.; Recht, L. Verubulin hydrochloride: apoptosis inducer vascular disrupting agent oncolytic. Drugs Future, 2010, 35, 993-997.
75. Spear, M.A.; LoRusso, P.; Mita, A.; Mita, M. Vascular disrupting agents (VDA) in oncology: advancing towards new therapeutic paradigms in the clinic. Curr. Drug Targets, 2011, 12, 2009-2015.
76. Patil, S.A.; Patil, R.; Pfeffer, L.M.; Miller, D.D. Chromenes: potential new chemotherapeutic agents for cancer. Future Med. Chem., 2013, 5, 1647-1660.
77. Cai, S.X. Small molecule vascular disrupting agents: potential new drugs for cancer treatment, a 2009 update. Front. Anti-Cancer Drug Discovery, 2010, 1, 380-427.
78. Kasibhatla, S.; Gourdeau, H.; Meerovitch, K.; Drewe, J.; Reddy, S.; Qiu, L.; Zhang, H.; Bergeron, F.; Bouffard, D.; Yang, Q.; Herich, J.; Lamothe, S.; Cai, S.X.; Tseng, B. Discovery and mechanism of action of a novel series of apoptosis inducers with potential vascular targeting activity. Mol. Cancer Ther., 2004, 3(11), 1365-1374.
79. Gourdeau, H.; Leblond, L.; Hamelin, B.; Desputeau, C.; Dong, K.; Kianicka, I.; Custeau, D.; Boudreau, C.; Geerts, L.; Cai, S.X.; Drewe, J.; Labrecque, D.; Kasibhatla, S.; Tseng, B. Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents. Mol. Cancer Ther., 2004, 3(11), 1375-1384.