ELR510444, a novel microtubule disruptor with multiple mechanisms of action

Journal of Pharmacology and Experimental Therapeutics

Volumn 336, Issue 3, 2011, Pages 652-660

  Risinger, A L ^a   Westbrook, C D ^a   Encinas, A ^b   Mulbaier M ^b   Schultes, C M ^b   Wawro, S ^b   Lewis, J D ^b   Janssen, B ^b   Giles, F J ^a   Mooberry, Susan L ^a  

^a Mays Cancer Center at UT Health San Antonio   (United States)

^b Elara Pharmaceuticals   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BETA TUBULIN; BETAIII TUBULIN; COLCHICINE; COMBRETASTATIN A4; ELR 510444; GLYCOPROTEIN P; N [2 [(4 HYDROXYPHENYL)AMINO] 3 PYRIDINYL] 4 METHOXYBENZENESULFONAMIDE; TUBULIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BINDING SITE; CANCER CELL; CANCER RESISTANCE; CELL PROLIFERATION; CELL SHAPE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DEPOLYMERIZATION; DOSE RESPONSE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG STRUCTURE; ENDOTHELIUM CELL; FEMALE; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; IC 50; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MICROTUBULE; MICROTUBULE ASSEMBLY; MITOSIS INHIBITION; MITOSIS SPINDLE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION; SINGLE DRUG DOSE; TUMOR VOLUME; TUMOR XENOGRAFT;

ANIMALS; APOPTOSIS; CELL CYCLE; CELL LINE; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; HELA CELLS; HUMANS; MICE; MICROTUBULES; MITOSIS; MITOTIC SPINDLE APPARATUS; RATS; SULFONAMIDES; SWINE; THIOPHENES; TUBULIN MODULATORS;

EID: 79951998753     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.175331     Document Type: Article

References (34)

1. Baluk P, Hashizume H, and McDonald DM (2005) Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15:102-111. (Pubitemid 40127638)
2. Banerjee A and Luduena RF (1992) Kinetics of colchicine binding to purified beta-tubulin isotypes from bovine brain. J Biol Chem 267:13335-13339.
3. Bhattacharyya B and Wolff J (1974) Promotion of fluorescence upon binding of colchicine to tubulin. Proc Natl Acad Sci USA 71:2627-2631.
4. Chen JG and Horwitz SB (2002) Differential mitotic responses to microtubule-stabilizing and -destabilizing drugs. Cancer Res 62:1935-1938.
5. Chiou JF, Liang JA, Hsu WH, Wang JJ, Ho ST, and Kao A (2003) Comparing the relationship of Taxol-based chemotherapy response with P-glycoprotein and lung resistance-related protein expression in non-small cell lung cancer. Lung 181:267-273.
6. Fojo T and Menefee M (2007) Mechanisms of multidrug resistance: the potential role of microtubule-stabilizing agents. Ann Oncol 18 (Suppl 5):v3-v8.
7. Gridelli C, Rossi A, Maione P, Rossi E, Castaldo V, Sacco PC, and Colantuoni G (2009) Vascular disrupting agents: a novel mechanism of action in the battle against non-small cell lung cancer. Oncologist 14:612-620.
8. Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, Jain RK, and McDonald DM (2000) Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol 156:1363-1380. (Pubitemid 30660013)
9. Horsman MR and Siemann DW (2006) Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies. Cancer Res 66:11520-11539. (Pubitemid 46094158)
10. Joe PA, Banerjee A, and Ludueña RF (2008) The roles of cys124 and ser239 in the functional properties of human betaIII tubulin. Cell Motil Cytoskeleton 65:476-486. (Pubitemid 351794103)
11. Jordan MA and Kamath K (2007) How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets 7:730-742.
12. Kang GJ, Getahun Z, Muzaffar A, Brossi A, and Hamel E (1990) N-acetylcolchinol O-methyl ether and thiocolchicine, potent analogs of colchicine modified in the C ring. Evaluation of the mechanistic basis for their enhanced biological properties. J Biol Chem 265:10255-10259.
13. Kanthou C and Tozer GM (2002) The tumor vascular targeting agent combretastatin A-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells. Blood 99:2060-2069. (Pubitemid 34525489)
14. Kanthou C and Tozer GM (2009) Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int J Exp Pathol 90:284-294.
15. Krishan A (1975) Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. J Cell Biol 66:188-193.
16. Lee L, Robb LM, Lee M, Davis R, Mackay H, Chavda S, Babu B, O'Brien EL, Risinger AL, Mooberry SL, et al. (2010) Design, synthesis, and biological evaluations of 2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoline analogs of combretastatin-A4. J Med Chem 53:325-334.
17. Leonard GD, Fojo T, and Bates SE (2003) The role of ABC transporters in clinical practice. Oncologist 8:411-424. (Pubitemid 37238869)
18. Luo Y, Hradil VP, Frost DJ, Rosenberg SH, Gordon GB, Morgan SJ, Gagne GD, Cox BF, Tahir SK, and Fox GB (2009) ABT-751, a novel tubulin-binding agent, decreases tumor perfusion and disrupts tumor vasculature. Anticancer Drugs 20: 483-492.
19. Pasquier E, Sinnappan S, Munoz MA, and Kavallaris M (2010) ENMD-1198, a new analogue of 2-methoxyestradiol, displays both antiangiogenic and vascular-disrupting properties. Mol Cancer Ther 9:1408-1418.
20. Rajkumar SV, Richardson PG, Lacy MQ, Dispenzieri A, Greipp PR, Witzig TE, Schlossman R, Sidor CF, Anderson KC, and Gertz MA (2007) Novel therapy with 2-methoxyestradiol for the treatment of relapsed and plateau phase multiple myeloma. Clin Cancer Res 13:6162-6167. (Pubitemid 350075076)
21. Risinger AL, Jackson EM, Polin LA, Helms GL, LeBoeuf DA, Joe PA, Hopper-Borge E, Ludueña RF, Kruh GD, and Mooberry SL (2008) The taccalonolides: microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms. Cancer Res 68:8881-8888.
22. Sève P and Dumontet C (2008) Is class III beta-tubulin a predictive factor in patients receiving tubulin-binding agents? Lancet Oncol 9:168-175. (Pubitemid 351150128)
23. Simmons TL, Nogle LM, Media J, Valeriote FA, Mooberry SL, and Gerwick WH (2009) Desmethoxymajusculamide C, a cyanobacterial depsipeptide with potent cytotoxicity in both cyclic and ring-opened forms. J Nat Prod 72:1011-1016.
24. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, and Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 82:1107-1112. (Pubitemid 20213250)
25. Tinley TL, Leal RM, Randall-Hlubek DA, Cessac JW, Wilkens LR, Rao PN, and Mooberry SL (2003a) Novel 2-methoxyestradiol analogues with antitumor activity. Cancer Res 63:1538-1549. (Pubitemid 36373641)
26. Tinley TL, Randall-Hlubek DA, Leal RM, Jackson EM, Cessac JW, Quada JC Jr, Hemscheidt TK, and Mooberry SL (2003b) Taccalonolides E and A: plant-derived steroids with microtubule-stabilizing activity. Cancer Res 63:3211-3220. (Pubitemid 36735874)
27. Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsk BM, Palme MH, et al. (2001) In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res 61:1013-1021. (Pubitemid 32174419)
28. Tozer GM, Prise VE, Wilson J, Cemazar M, Shan S, Dewhirst MW, Barber PR, Vojnovic B, and Chaplin DJ (2001) Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability. Cancer Res 61:6413-6422. (Pubitemid 32785286)
29. Trock BJ, Leonessa F, and Clarke R (1997) Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst 89:917-931. (Pubitemid 27282064)
30. Walter-Yohrling J, Morgenbesser S, Rouleau C, Bagley R, Callahan M, Weber W, and Teicher BA (2004) Murine endothelial cell lines as models of tumor endothelial cells. Clin Cancer Res 10:2179-2189. (Pubitemid 38375580)
31. Weiderhold KN, Randall-Hlubek DA, Polin LA, Hamel E, and Mooberry SL (2006) CB694, a novel antimitotic with antitumor activities. Int J Cancer 118:1032-1040. (Pubitemid 43157682)
32. Yee KW, Hagey A, Verstovsek S, Cortes J, Garcia-Manero G, O'Brien SM, Faderl S, Thomas D, Wierda W, Kornblau S, et al. (2005) Phase 1 study of ABT-751, a novel microtubule inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res 11:6615-6624. (Pubitemid 41339002)
33. Yeung SC, She M, Yang H, Pan J, Sun L, and Chaplin D (2007) Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. J Clin Endocrinol Metab 92:2902-2909. (Pubitemid 47236348)
34. Yoshimatsu K, Yamaguchi A, Yoshino H, Koyanagi N, and Kitoh K (1997) Mechanism of action of E7010, an orally active sulfonamide antitumor agent: inhibition of mitosis by binding to the colchicine site of tubulin. Cancer Res 57:3208-3213. (Pubitemid 27351737)