Tubulin inhibitors: A patent review

Expert Opinion on Therapeutic Patents

Volumn 24, Issue 1, 2014, Pages 69-88

  Liu, Yi Min ^a   Chen, Hsiao Ling ^a   Lee, Hsueh Yun ^a   Liou, Jing Ping ^a  

^a TAIPEI MEDICAL UNIVERSITY   (Taiwan)

Author keywords

Cancer; Combretastatin; Microtubule; Mitosis; Tubulin; Vascular disrupting

Indexed keywords

ANG 1005; ANTINEOPLASTIC AGENT; BPROLO 75; CA 4 P; CA 4P; COLCHICINE DERIVATIVE; COMBRETASTATIN A1 PHOSPHATE; COMBRETASTATIN A4; DOCETAXEL; E 7974; EPOTHILONE B; EPOTHILONE DERIVATIVE; ER 086526; ERIBULIN; INDIBULIN; IXABEPILONE; LAULIMALIDE; N [2 [(4 HYDROXYPHENYL)AMINO] 3 PYRIDINYL] 4 METHOXYBENZENESULFONAMIDE; NAVELBINE; OMBRABULIN; PACLITAXEL; PACLITAXEL POLIGLUMEX; PROTEIN INHIBITOR; SAGOPILONE; TUBULIN INHIBITOR; TUBULYSIN A; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINBLASTINE; VINCRISTINE; VINDESINE; VINFLUNINE; XPR 9881;

ANTINEOPLASTIC ACTIVITY; BINDING AFFINITY; BINDING SITE; ER 086526; HUMAN; MICROTUBULE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN POLYMERIZATION; REVIEW; TARGET CELL;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; HUMANS; LEGISLATION, DRUG; MICROTUBULES; MOLECULAR STRUCTURE; NEOPLASMS; PATENTS AS TOPIC; STRUCTURE-ACTIVITY RELATIONSHIP; TUBULIN MODULATORS;

EID: 84890407835     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2014.859247     Document Type: Review

References (130)

1. Zhou J, Giannakakou P. Targeting microtubules for cancer chemotherapy. Curr Med Chem Anti Cancer Agents 2005;5:65-71
2. Risinger AL, Giles FJ, Mooberry SL. Microtubule dynamics as target in oncology. Cancer Treat Rev 2009;35:255-61
3. Imoto Y, Yoshida Y, Yagisawa F, et al. The cell cycle, including the mitotic cycle and organelle division cycles, as revealed by cytological observations. J Electron Microsc 2011;60(S1):S117-36
4. Nogales E, Whittaker M, Milligan RA, Downing KH. High-resolution model of the microtubule. Cell 1999;96:79-88
5. Amos LA. What tubulin drugs tell us about microtubule structure and dynamics. Semin Cell Dev Biol 2011;22:916-26
6. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004;4:253-65
7. Kavallaris M. Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer 2010;10:1-11
8. Denekamp J. Vascular attack as a therapeutic strategy for cancer. Cancer Metastasis Rev 1990;9:267-82
9. Thorpe PE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res 2004;10:415-27
10. Siemann DW, Horsman MR. Vascular targeted therapies in oncology. Cell Tissue Res 2009;335:241-8
11. Siemann DW. The unique characteristics of tumor vasculature and preclinical evidence for its selective disruption by tumor-vascular disrupting agents. Cancer Treat Rev 2011;37:63-74
12. McKeage MJ, Baguley BC. Disrupting established tumor blood vessels. Cancer 2010;116:1859-71
13. Dumontet C, Jordan MN. Microtubule-binding agents: A dynamic field of cancer therapeutics. Nat Rev Drug Discov 2010;9:790-803
14. Prota AE, Bargsten K, Zurwerra D, et al. Molecular mechanism of action of microtubule-satbilizing anticancer agents. Science 2013;339:587-60
15. Chen J-G, Horwitz SB. Differential mitotic responses to microtubulestabilizing and -destabilizing drugs. Cancer Res 2002;62:1935-8
16. Perez EA. Microtubule inhibitors: Differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance. Mol Cancer Ther 2009;8:2086-95
17. Yue Q-X, Liu X, Guo D-A. Microtubule-binding natural products for cancer therapy. Planta Med 2010;76:1037-43
18. Kingston DGI. Tubulin-interactive natural products as anticancer agents. J Nat Prod 2009;72:507-15
19. Campos SM, Dizon DS. Antimitotic inhibitors. Hematol Oncol Clin N Am 2012;26:607-28
20. Cutts JH, Beer CT, Noble RL. Biological properties of vincaleukoblastine, an alkaloid in Vinca rosea Linn, with reference to its antitumor action. Cancer Res 1960;20:1023-31
21. Gupta S, Bhattacharyya B. Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem 2003;253:41-7
22. Kuznetsov G, TenDyke K, Towle MJ, et al. Tubulin-based antimitotic mechanism of E7974, a novel analogue of the marine sponge natural product hemiasterlin. Mol Cancer Ther 2009;8:2852-60
23. Sasse F, Steinmetzm H, Heil J, et al. Tubulysins, new cytostatic peptides from myxobacteria acting on microtubule production, isolation, physic-chemical and biological properties. J Antibiot (Tokyo) 2000;53:879-85
24. Khalil MW, Sasse F, Lu?nsdorf H, et al. Mechanism of action of tubulysin, an antimitotic peptide from myxobacteria. ChemBioChem 2006;7:678-83
25. Zeino M, Zhao Q, Eichhorn T, et al. Molecular docking studies of myxobacterial disorazoles and tubulysins to tubulin. J Biosci Med 2013;3:37-44
26. Kaur G, Hollingshead M, Holbeck S, et al. Biological evaluation of tubulysin A: A potential anticancer and antiangiogenic natural product. Biochem J 2006;396:235-42
27. Wilson L, Meza I. The mechanism of action of colchicine. J Cell Biol 1973;58:709-19
28. Babttacharyya B, Panda D, Gupta S, Banerjee M. Anti-mitotic activity of colchicine and the structural basis for its interaction with tubulin. Med Res Rev 2008;28:155-83
29. Uppuluri S, Knipling L, Sackett DL, Wolff J. Localization of the colchicinebinding site of tubulin. Proc Natl Acad Sci USA 1993;90:11598-602
30. Colchicine (marketed as Colcrys) information. FDA Public Health Advisory. Washington, DC: FDA/Center for Drug Evaluation and Reasearch, 2005.Available from: Www.fda.gov/ Drugs/DrugSafety/Postmarket DrugSafetyInformationforPatientsand Providers/ucm174382.htm [Last accessed 18 August 2013]
31. Lu Y, Chen J, Xiao M, Miller DD. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res 2012;29:2943-71
32. Massarotti A, Coluccia A, Silvestri R, et al. The tubulin colchicine domain: A molecular modeling perspective. ChemMedChem 2012;7:33-42
33. Pettit GR, Cragg GM, Herald DL, et al. Isolation and structure of combretastatin. Can J Chem 1982;60:1374-6
34. Pettit GR, Singh SB, Niven ML, 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 1987;50:119-31
35. Shen C-H, Shee J-J, Wu J-Y, et al. Combretastatin A-4 inhibits cell growth and metastasis in bladder cancer cells and retards tumour growth in a murine orthotopic bladder tumour model. Br J Pharmacol 2010;160:2008-27
36. Young SL, Chaplin DJ. Combretastatin A4 phosphate: Background and current clinical ststus. Expert Opin Investig Drugs 2004;13:1171-82
37. Siemann DW, Chaplin DJ, Walicke PA. A review and update of the current status of the vasculature disabling agent combrestatin-A4 phosphate (CA4P). Expert Opin Investig Drugs 2009;18:189-97
38. Delmonte A, Sessa C. AVE8062: A new combretastatin derivative vascular disrupting agent. Expert Opin Investig Drugs 2009;18:1541-8
39. Chaplin DJ, Hill SA. The development of combretastatin A4 phosphate as a vascular targeting agent. Int J Radiat Oncology Biol Phys 2002;54:1491-6
40. Heath VL, Bicknell R. Anticancer strategies involving the vasculature. Nat Rev Clin Oncol 2009;6:395-404
41. Kanthou C, Tozer GM. Microtubule depolymerizing vascular disrupting agents: Novel therapeutic agents for oncology and other pathologies. Int J Exp Pathol 2009;90:284-94
42. Salmon HW, Siemann DW. Effect of the second-generation vascular disrupting agent OXi4503 on tumor vascularity. Clin Cancer Res 2006;12:4090-4
43. Patterson DM, Zweifel M, Middleton MR, et al. Phase I Clinical and pharmacokinetic evaluation of the vascular disrupting agent OXi4503 in patients with advanced solid tumors. Clin Cancer Res 2012;18:1415-25
44. Liou J-P, Chang Y-L, Kuo F-M, et al. Concise synthesis and structure-Activity relationships of combretastatin A-4 analogues, 1-Aroylindoles and 3- Aroylindoles, as novel classes of potent antitubulin agents. J Med Chem 2004;47:4247-57
45. Kuo C-C, Hsieh H-P, Pan W-Y, et al. BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer res 2004;64:4621-8
46. Wang X, Wu E, Wu J, et al. An antimitotic and antivascular agent BPR0L075 overcomes multidrug resistance and induces mitotic catastrophe in paclitaxel-resistant ovarian cancer cells. PLoS One 2013;8:e65686
47. Liu L, Beck H, Wang X, et al. Tubulin-destabilizing agent BPR0L075 induces vascular-disruption in human breast cancer mammary fat pad xenografts. PLoS One 2012;7:e43314
48. Chen C-P, Hu C-B, Yeh K-C, et al. Antiangiogenic activites and cisplatincombined antitumor activities of BPR0L075. Anticancer Res 2010;30:2813-22
49. Yee KWL, Hagey A, Verstovsek S, et al. Phase 1 study of ABT-751, a novel microtubule inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res 2005;11:6615-24
50. Hande KR, Hagey A, Berlin J, et al. The pharmacokinetics and safety of ABT-751, a novel, orally bioavailable sulfonamide antimitotic agent: Results of a phase 1 study. Clin Cancer Res 2006;12:2834-40
51. Fox E, Maris JM, Widemann BC, et al. A phase 1 study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors. Clin Cancer Res 2008;14:1111-15
52. Mauer AM, Cohen EEW, Ma PC, et al. A phase II study of ABT-751 in patients with advanced non-small cell lung cancer. J Thorac Oncol 2008;3:631-6
53. Rudin CM, Mauer A, Smakal M, et al. Phase I/II study of pemetrexed with or without ABT-751 in advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2011;29:1075-82
54. Bacher G, Beckers T, Emig P, et al. New small-molecule tubulin inhibitors. Pure Appl Chem 2001;73:1459-64
55. Bacher G, Nickel B, Emig P, et al. D- 24851, a novel synthetic microtubule inhibitor, exerts curative antitumoral activity in vivo, shows efficacy toward multidrug-resistant tumor cells, and lacks neurotoxicity. Cancer Res 2001;61:392-9
56. Wienecke A, Bacher G. Indibulin, a novel microtubule inhibitor, discriminates between mature neuronal and nonneuronal tubulin. Cancer Res 2009;69:171-7
57. Kuppens IELM, Witteveen PO, Schot M, et al. Phase I dose-finding and pharmacokinetic trial of orally administered indibulin (D-24851) to patients with solid tumors. Invest New Drugs 2007;25:227-35
58. Oostendorp RL, Witteveen PO, Schwartz B, et al. Dose-finding and pharmacokinetic study of orally administered indibulin (D-24851) to patients with advanced solid tumors. Invest New Drugs 2010;28:163-70
59. Wani MC, Taylor HL, Wall ME, et al. Plant antitumor agents. VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971;93:2325-7
60. Nogales E, Wolf SG, Khan IA, et al. Structure of tubulin at 6.5 A ° and location of the taxol-binding site. Nature 1995;375:424-7
61. Wall ME, Wani MC. Camptothecin and taxol: Discovery to clinic-Thirteenth bruce F. cain memorial award lecture. Cancer Res 1995;55:753-60
62. Yvon A-MC, Wadsworth P, Jordan MA. Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol Biol Cell 1999;10:947-59
63. Amos LA, Lowe J. How Taxol stabilizes microtubule structure. Chem Biol 1999;6:R65-9
64. Magnani M, Maccari G, Andreu JM, et al. Possible binding site for paclitaxel at microtubule pores. FEBS J 2009;276:2701-12
65. Morris PG, Fornier MN. Microtubule active agents: Beyond the taxane frontier. Clin Cancer Res 2008;14:7167-72
66. van Zuylen L, Verweij J, Sparreboom A. Role of formulation vehicles in taxane pharmacology. Invest New Drugs 2001;19:125-41
67. Miele E, Spinelli GP, Miele E, et al. Albumin-bond formulation of paclitaxel (Abraxane- ABI-007) in the treatment of breast cancer. Int J Nanomedicine 2009;4:99-105
68. Paz-Ares L, Ross H, O'Brien M, et al. Phase III trial comparing paclitaxel poliglumex vs docetaxel in the secondline treatment of non-small-cell lung cancer. Br J Cancer 2008;98:1608-13
69. Langer CJ, O'Byrne KJ, Socinski MA, et al. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-nai?ve advanced non-small cell lung cancer. J Thorac Oncol 2008;3:623-30
70. Régina A, Demeule M, Ché C, et al. Antitumour activity of ANG 1005, a conjugate between paclitaxel and the new brain delivery vector angiopep-2. Br J Pharmacol 2008;155:185-97
71. Kurzrock R, Gabrail N, Chandhasin C, et al. Safety, pharmacokinetics, and activity of GRN1005, a novel conjugate of angiopep-2, a peptide facilitating brain penetration, and paclitaxel, in patients with advanced solid tumors. Mol Cancer Ther 2012;11:308-16
72. Ferron GM, Dai Y, Semiond D. Population pharmacolinetics of cabazitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol 2013;71:681-92
73. Yamamoto N, Boku N, Minami H. Phase I study of larotaxel administered as a 1-h intravenous infusion every 3 weeks to Japanese patients with advanced solid tumours. Cancer Chemother Pharmacol 2009;65:129-36
74. Diéras V, Limentani S, Romieu G, et al. Phase II multicancer study of larotaxel (XPR9881), a novel taxoid, in patients with metastatic breast cancer who previously received taxane-based therapy. Ann Oncol 2008;19:1255-60
75. Bollag DM, McQueney PA, Zhu J, et al. Epothilones, a new class of microtubulestabilizing agents with a taxol-like mechanism of action. Cancer Res 1995;55:2325-33
76. Bode CJ, Gupta ML Jr, Reiff EA, et al. Epothilone and paclitaxel: Unexpected differences in promoting the assembly and stabilization of yeast microtubules. Biochemistry 2004;41:3870-4
77. Khrapunovich-Baine M, Menon V, Yang C-PH, et al. Hallmarks of molecular action of microtubule stabilizing agents: Effects of epothilone B, ixabepilone, peloruside A, and laulimalide on microtubule conformation. J Biol Chem 2011;286:11765-78
78. Hunt JT. Discovery of ixabepilone. Mol Cancer Ther 2009;8:275-81
79. Cortes J, Vidal M. Beyond taxanes: The next generation of microtubule-Targeting agents. Breast Cancer Res Treat 2012;133:821-30
80. Ferrandina G, Mariani M, Andreoli M, et al. Novel drugs targeting microtubules: The role of epothilones. Curr Pharm Des 2012;18:2793-803
81. Cheng KL, Bradley T, Budman DR. Novel microtubule-Targeting agents- The epothilones. Biol Targets Ther 2008;2:789-811
82. DeConti RC, Algazi AP, Andrews S, et al. Phase II trial of sagopilone, a novel epothilone analog in metastatic melanoma. Br J Cancer 2010;103:1548-53
83. McMeekin S, Patel R, Verschraegen C, et al. Phase I/II study of sagopilone (ZKEPO) plus carboplatin in women with recurrent platinum-sensitive ovarian cancer. Br J Cancer 2012;106:70-6
84. Beer TM, Smith DC, Hussain A, et al. Phase II study of first-line sagopilone plus prednisone in patients with castration-resistant prostate cancer: A phase II study of the department of defense prostate cancer clinical trials consortium. Br J Cancer 2012;107:808-13
85. Corley DG, Herb R, Moore RE, et al. Laulimalides. New potent cytotoxic macrolides from a marine sponge and a nudibranch predator. J Org Chem 1988;53:3644-6
86. Quinoa E, Kakou Y, Crews P. Fijianolides, polyketide heterocycles from a marine sponge. J Org Chem 1988;53:3642-4
87. Mooberry SL, Tien G, Hernandez AH, et al. Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. Cancer Res 1999;59:653-60
88. Mulzer J,Ohler E. Microtubule-stabilizing marine metabolite laulimalide and its derivatives: Synthetic approaches and antitumor activity. Chem Rev 2003;103:3753-86
89. Pryor DE, O'Brate A, Bilcer G, et al. The microtubule stabilizing agent laulimalide dose not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. Biochemistry 2002;41:9109-15
90. Pineda O, Farràs J, Maccari L, et al. Computational comparison of microtubule-stabilising agents laulimalide and peloruside with taxol and colchicine. Bioorg Med Chem Lett 2004;14:4825-9
91. Bennett MJ, Barakat K, Huzil JT, et al. Discovery and characterization of the laulimalide-microtubule binding mode by mass shift perturbation mapping. Chem Biol 2010;17:725-34
92. Gapud EJ, Bai R, Ghosh AK, Hamel E. Laulimalide and paclitaxel: A comparison of their effects on tubulin assembly and their synergistic action when present simultaneously. Mol Pharmacol 2004;66:113-21
93. Liu J, Towle MJ, Cheng H, et al. In vitro and in vivo anticancer activities of synthetic (-)-laulimalide, a marine natural product microtubule stabilizing agent. Anticancer Res 2007;27:1509-18
94. Hood KA, West LM, Rouwé B, et al. Peloruside A, a novel antimitotic agent with paclitaxel-like microtubulestabilizing activity. Cancer Res 2002;62:3356-60
95. Gaitanos TN, Buey RM, Díaz JF, et al. Peloruside A dose not bind to the taxoid site on b-Tubulin and trtains its activity in multidrug-resistant cell lines. Cancer Res 2004;64:5063-7
96. Nguyen TL, Xu X, Gussio R, et al. The assembly-inducing laulimalide/peloruside A binding site on tubulin: Molecular modeling and biochemical studies with [3H] peloruside A. J Chem Inf Model 2010;50:2019-28
97. Hamel E, Day BW, Miller JH, et al. Synergistic effects of peloruside A and laulimalide with taxoid site drugs, but not with each other, on tubulin assembly. Mol Pharmacol 2006;70:1555-64
98. Chaplin JH, Gill GS, Grobelny DW, et al. inventors; Bionomics Ltd, assignee. Substituted benzofurans, benzothiophenes, benzoselenophenes and indoles and their use as tubulin polymerization inhibitors. US0053351A1; 2013
99. Bernard Luke Flynn; inventors; Bionomics Ltd, assignee. Chemical processes for the manufacture of substituted benzofurans. WO006686A1; 2012
100. Chaplin JH, Gill GS, Grobelny DW, Flynn BL; inventors; Bionomics Ltd, assignee. Novel tubulin polymerization inhibitors. US0309768A1; 2012
101. Leblond B, Taverne T, Beausoleil E, et al. inventors; Exonhit S.A., assignee. Substituted isoquinolines and their use as tubulin polymerization inhibitors. WO151423A1; 2011
102. Leblond B, Taverne T, Beausoleil E, et al. inventors; Exonhit S.A., assignee. Substituted isoquinolines and their use as tubulin polymerization inhibitors. US0131018A1; 2013
103. Liou J-P, Chang J-Y; inventors; Taipei medical university, National health research institutes, assignee. Aroylquinoline compounds. TW201138772A1; 2011
104. Dalton JT, Miller DD, Sunjoo AHN, et al. inventors. Indoles, derivatives and analogs thereof and uses therefor. US0022121A1; 2012
105. Sun L, Jiang J, Borella C, et al. inventors; Synta Pharmaceuticals Corp. assignee. Compounds for the treatment of proliferative disorders. US0040937A1; 2012
106. Sun L, Borella C, Li H, et al. inventors; Synta Pharmaceuticals Corp. assignee. Compounds for the treatment of proliferative disorders. US0059893A1; 2011
107. Liu Z, Liu L, Han Y, et al. inventors; Institute of medicinal biotechnology Chinese academy of medical sciences, assignee. Substituted biaryl-methylene-cycloalkyl derivatives and its preparations and applications. CN102786394A; 2012
108. Negi AS, Prakasham AP, Saxena AK, et al. inventors; Council of scientific and industrial research, assignee. Anticancer and tubulin polymerization inhibition activity of benzylidene indanones and process of preparing the same. US0079396A1; 2013
109. Walsh JJ, Shah R, Mccormack EM, et al. inventors; The provost, fellows, foundation scholars, and the other members of board, of the college of the holy and undivided trinity of Queen Elizabeth, near Dublin, assignee. Tubulin binding agents. WO026942A1; 2013
110. Nickel B, Bacher G, Klenner T, et al. inventors. Indolyl-3-glyoxylic acid derivatives having therapeutically valuable properties. US0057124A1; 2008
111. Wallner BP, Schwartz BE, Marnitsky PB, et al. inventors; Ziopharm oncology, Inc., assignee. Use of indolyl-3-glyoxylic acid derivatives including indibulin, alone or in combination with further agents for treating cancer. WO066807A1; 2008
112. Wang Y, Zhang C, Liu XR, et al. inventors; Nanjing Sanhome pharmaceutical Co., Ltd, assignee. Tumor targeting drugs C-A4 derivatives. CN102863388A; 2013
113. Edwards ML, Stemerick DM, Sunkara PS. Chalcones: A new class of antimitotic agents. J Med Chem 1990;33:1948-54
114. Boumendjel A, Boccard J, Carrupt P-A, et al. Antimitotic and antiproliferative activities of chalcones: Forward structureactivity relationship. J Med Chem 2008;51:2307-10
115. Lin C-N, Tu H-Y, Huang A-M, et al. inventors; Kaohsiung medical university, assignee. Synthesis and biological evaluation of 2',5'-dimethoxychalcone derivatives as microtubule-Targeted anticancer agents. TW201143765A1; 2011
116. Scozzafava A, Carta F, Supuran CT. Secondary and tertiary sulfonamides: A patent review (2008-2012). Expert Opin Ther Patent 2013;23:203-13
117. Zhu HL, Luo Y, Qiu KM; inventors; Nanjing university, assignee. Preparation of cinnamoyl sulfonamide derivatives and the application in anticancer drugs. CN102838515A; 2012
118. Freyne EJE, Mevellec LA, Vialard JE, et al. inventors; Janssen pharmaceutica NV, assignee. Quinazolinone derivatives as tubulin polymerization inhibitors. WO118384A1; 2009
119. Angibaud PR, Mevellec LA, Roux B, et al. inventors; Janssen-Cilag, Janssen pharmaceutica NV, assignee. Tetrahydrophenanthridinones and tetrahydrocyclopenta quinolinones as PARP and tubulin polymerization inhibitors. US0263622A1; 2011
120. Burns CJ, Wilks AF, Harte MF, et al. inventors; Cytopia research Pty Ltd, assignee. Tubulin inhibitors. US0269760A1; 2011
121. Chen M-H, Chuang S-H, Chen Y-J, et al. inventors; Development center for biotechnology, assignee. Novel tubulin inhibitors and methods of using the same. WO092471A2; 2012
122. Richter W; inventors; R&D Biopharmaceuticals Gmbh, assignee. Tubulin inhibitors. WO057805A1; 2011
123. Richter W; inventors; R&D Biopharmaceuticals Gmbh, assignee. Tubulin inhibitors. US0252739A1; 2012
124. Langenhan JM, Peters NR, Guzei IA, et al. Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization. Proc Natl Acad Sci USA 2005;102:12305-10
125. Thorson JS, Ahmed A; inventors; Wisconsin alumni research foundation, assignee. Colchicine neoglycosides and methods for their synthesis and use. WO067039A2; 2008
126. Landen JW, Lang R, McMahon SJ, et al. Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma. Cancer Res 2002;62:4109-14
127. Joshi HC, Aneja R, Vangapandu SN; inventors; Emory universicy, assignee. 9-Aminonoscapine and its use in treating cancers, including drug-resistant cancer. WO028259A2; 2010
128. Lane HA, Bachmann F; inventors; Basilea pharmaceutica AG, assignee. Use of acetylated tubulin as a biomarker of drug response to furazanobenzimidazoles. WO113802A1; 2012
129. Pohlmann J, Bachmann F; inventors; Basilea pharmaceutica AG, assignee. Furazanobenzimidazoles as prodrugs to treat neoplastic or autoimmune diseases. US0264792A1; 2012
130. Bachmann F, Burger K, Pohlmann J, et al. Abstract C229: BAL27882: A novel anticancer agent which dissociates microtubules and creates a distinct cellular phenotype. Mol Cancer Ther 2009;8(12 Suppl):C229