Recent developments in the chemical biology of epothilones

Current Pharmaceutical Design

Volumn 11, Issue 13, 2005, Pages 1595-1613

  Altmann, Karl Heinz ^a  

^a ETH ZURICH   (Switzerland)

Author keywords

Anticancer; Antiproliferative; Drug discovery; Epothilone; Medicinal chemistry; Microtubule stabilizer; Natural products; Structure activity relationship

Indexed keywords

ABJ 879; ANTINEOPLASTIC AGENT; AZIRIDINE DERIVATIVE; BMS 310705; CYCLOPROPANE DERIVATIVE; DOCETAXEL; EPOTHILONE A; EPOTHILONE B; EPOTHILONE C; EPOTHILONE D; EPOTHILONE DERIVATIVE; IMATINIB; IXABEPILONE; PACLITAXEL; TUBULIN; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; BREAST TUMOR; CANCER CELL CULTURE; CANCER INHIBITION; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CLINICAL TRIAL; COLON CARCINOMA; CONCENTRATION (PARAMETERS); CONCENTRATION RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG STRUCTURE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MICROTUBULE ASSEMBLY; NONHUMAN; OVARY TUMOR; PRIORITY JOURNAL; REVIEW; STRUCTURE ANALYSIS;

ANTINEOPLASTIC AGENTS; DRUG DESIGN; EPOTHILONES; HUMANS; MOLECULAR CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP; TUBULIN;

EID: 18744390786     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/1381612053764715     Document Type: Review

References (136)

1. Lu MC. In Foye WO Ed. Cancer Chemotherapeutic Agents. Washington, DC, American Chemical Society 1995; 345-368.
2. (a) Mekhail TM, Markman M. Paclitaxel in cancer therapy. Expert opinion on pharmacotherapy 2002; 3: 755-766.
3. (b) Obasaju C, Hudes GR. Paclitaxel and docetaxel in prostate cancer. Hematology/oncology clinics of North America 2001; 15: 525-545.
4. Hamel E. Antimitotic natural products and their interaction with tubulin. Med Res Rev 1996; 16:207-231.
5. Rowinsky EK. The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Ann Rev Med 1997; 48: 353-374.
6. Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. 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.
7. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979; 277: 665-667.
8. (a) Höfle G, Bedorf N, Gerth K, Reichenbach, H. German Patent Disclosure, DE 4138042, 1993;
9. Höfle G, Bedorf N, Gerth K, Reichenbach, H. Chem Abstr 1994; 120: 52841.
10. (b) Gerth K, BedorfN, Höfle G, Irschik H, Reichenbach H. Epothilons A and B - antifungal and cytotoxic compounds from Sorangium cellulosum (cyxobacteria) - Production, physico-chemical and biological Properties. J Antibiotics 1996; 49: 560-564.
11. Bollag DM, McQueney PA, Zhu J, Hensens O, Koupal L, Liesch J, et al. Epothilones, a new class of microtubule-stabilizing agents with a Taxol-like mechanism of action. Cancer Res 1995; 55: 2325-2333.
12. Hardt IH, Steinmetz H, Gerth K, Sasse F, Reichenbach H, Höfle G. New Natural Epothilones from Sorangium cellulosum, Strains So ce90/B2 and So ce90/D13: Isolation, Structure Elucidation, and SAR Studies. J Nat Prod 2001; 64: 847-856.
13. Höfle G, Bedorf N, Steinmetz H, Schomburg D, Gerth K, Reichenbach, H. Antibiotics from gliding bacteria. 77. Epothilone A and B - novel 16-membered macrolides with cytotoxic activity: isolation, crystal structure, and conformation in solution. Angew Chem Int Ed Engl 1996; 35: 1567-1569.
14. (a) Discodermolide: ter Haar E, Kowalski RJ, Hamel E, Lin CM, Longley RE, Gunasekara SP, et al. Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. Biochemistry 1996; 35: 243-250.
15. (b) Eleutherobin: Long BH, Carboni JM, Wasserman AJ, Cornell LA, Cassaza AM, Jensen PR, et al. Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol). Cancer Res 1998; 58:1111-1115.
16. (c) Laulimalide: Mooberry SL, Tien G, Hernandez AH, Plubrurkan A, Davidson BS. Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. Cancer Res 1999; 59: 653-660).
17. (d) Peloruside: Hood KA, West LM, Rouwe B, Northcote PT, Berridge MV, Wakefield StJ, et al. Peloruside A, a Novel Antimitotic Agent with Paclitaxel-like Microtubule-stabilizing Activity. Cancer Res 2002; 62: 3356-3360.
18. Dictyostatin: Isbrucker A, Cummins J, Pomponi S, Longley RE, Wright AE. Tubulin polymerizing activity of dictyostatin-1, a polyketide of marine sponge origin. Biochem Pharmacol 2003; 66: 75-82.
19. Kowalski RJ, Giannakakou P, Hamel E. Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol). J Biol Chem 1997; 272:2534-2541.
20. Altmann K-H, Wartmann M, O'Reilly T. Epothilones and related structures - a new class of microtubule inhibitors with potent in vivo antitumor activity. Biochim Biophys Acta 2000; 1470: M79-M91.
21. Wolff A, Technau A, Brandner G. Epothilone A induces apoptosis in neuroblastoma cells with multiple mechanisms of drug resistance. International Journal of Oncology 1997; 11: 123-126.
22. Giannakakou P, Sackett DL, Kang YK, Zhan Z, Buters JT, Fojo T, et al. Paclitaxel-resistant human ovarian cancer cells have mutant β-tubulins that exhibit impaired paclitaxel-driven polymerization. J Biol Chem 1997; 272:17118-17125.
23. Nicolaou KC, Roschangar F, Vourloumis D. Chemical biology of epothilones. Angew Chem Int Ed Engl 1998; 37: 2014-2045.
24. Harris CR, Danishefsky SJ. Complex Target-Oriented Synthesis in the Drug Discovery Process: A Case History in the dEpoB Series. J Org Chem 1999; 64: 8434-8456.
25. Mulzer J, Martin HJ, Berger M. Progress in the synthesis of chiral heterocyclic natural products: epothilone B and tartrolon B. J Heterocycl Chem 1999; 36: 1421-1436.
26. Nicolaou KC, Ritzen A, Namoto K. Recent developments in the chemistry, biology and medicine of the epothilones. JCS Chem Commun 2001; 1523-1535.
27. (a) Liu Z-Y, Chen Z-C, Yu C-Z, Wang R-F, Zhang RZ, Huang C-S, et al. Total synthesis of epothilone A through stereospecific epoxidation of the p-methoxybenzyl ether of epothilone C. Chemistry - A European Journal 2002; 8: 3747-3756.
28. (b) Liu J, Wong C-H. Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem Intl Ed Engl 2002; 41: 1404-1407.
29. (c) Sun J, Sinha SC. Stereoselective total synthesis of epothilones by the metathesis approach involving C9-C10 bond formation. Angew Chem Intl Ed Engl 2002; 41: 1381-1383.
30. (d) Ermolenko MS, Potier P. Synthesis of epothilones B and D from D-glucose. Tetrahedron Lett 2002; 43: 2895-2898.
31. (e) Martin N, Thomas EJ. Total syntheses of epothilones Band D: applications of allylstannanes in organic synthesis. Tetrahedron Lett 2001; 42: 8373-8377.
32. (f) Valluri M, Hindupur RM, Bijoy, P, Labadie G, Jung J-C, Avery M.A. Total synthesis of epothilone B. Organic Letters 2001; 3: 3607-3609.
33. (g) Hindupur RM, Panicker B, Valluri M, Avery MA. Total synthesis of epothilone A. Tetrahedron Lett 2001; 42: 7341-7344.
34. Wartmann M, Altmann K-H. The biology and medicinal chemistry of epothilones. Currr Med Chem Anti-Cancer Agents 2002; 2:123-148.
35. Altmann K-H. Epothilone B and its analogs - a new family of anticancer agents. Mini-Rev Med Chem 2003; 3: 149-158.
36. Borzilleri RM, Vite GD. Epothilones: new tubulin polymerization agents in preclinical and clinical development. Drugs of the Future 2003; 27: 1149-1163.
37. Chappell MD, Stachel SJ, Lee CB, Danishefsky SJ. En route to a plant scale synthesis of the promising antitumor agent 12,13-desoxyepothilone B. Org Lett 2002; 2: 1633-1636.
38. Altmann K-H, Bold G, Caravatti G, End N, Flörsheimer A, Guagnano V, et al. Epothilones and their analogs - potential new weapons in the fight against cancer. Chimia 2000; 54: 612-621.
39. For a recent review on epothilone biosynthesis cf.: Walsh CT, O'Connor S, Schneider TL. Polyketide-nonribosomal peptide epothilone antitumor agents: the EpoA, B, C subunits. J. Ind Microbiol Biotechnol 2003; 30:448-455
40. He L, Orr GA, Horwitz SB. Novel molecules that interact with microtubules and have functional activity similar to Taxol. Drug Discovery Today 2001; 6:1153-1164.
41. Altaha R, Fojo T, Reed E, Abraham J. Epothitones: A novel class of non-taxane microtubule-stabilizing agents. Curr Pharm Des 2002; 8: 1707-1712.
42. Buey RM, Diaz JF, Andreu JM, O'Brate A, Giannakakou P, Nicolaou KC, et al. Interactions of Epothilone Analogs with the Paclitaxel Binding Site: Relationship between Binding Affinity, Microtubule Stabilization, and Cytotoxicity. Chem & Biol 2004; 11: 225-236.
43. Jordan MA, Wendell K, Gardiner S, Derry WB, Copp H, Wilson L. Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exist and apoptotic cell death. Cancer Res 1996; 56: 816-825.
44. Lichtner RB, Rotgeri A, Bunte T, Buchmann B, Hoffmann J, Schwede W, et al. Subcellular distribution of epothilones in human tumor cells. Proc Natl Acad Sci USA 2001; 98:11743-11748.
45. Jordan MA. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem: Anti-Cancer Agents 2002; 2: 1-14.
46. Kamath K, Jordan MA. Suppression of microtubule dynamics by epothilone B is associated with mitotic arrest. Cancer Res 2003; 63: 6026-6031.
47. Chen J-GC, Horwitz SB. Differential mitotic responses to microtubule-stabilizing and -destabilizing drugs. Cancer Res 2002; 14: 1935-1938.
48. Chen J-GC, Yang C-PHY, Cammer M, Horwitz SB. Gene Expression and Mitotic Exit Induced by Microtubule-Stabilizing Drugs. Cancer Res 2003; 15: 7891-7899.
49. Wittmann S, Bali P, Donapaty S, Nimmanapallli R, Guo F, Yamaguchi H, et al. Flavopiridol Down-Regulates Antiapoptotic Proteins and Sensitizes Human Breast Cancer Cells to Epothilone B-induced Apoptosis. Cancer Res 2003; 63: 93-99.
50. McDaid HM, Horwitz SB. Selective Potentiation of Paclitaxel (Taxol)-Induced Cell Death by Mitogen-Activated Protein Kinase Kinase Inhibition in Human Cancer Cell Lines. Mol Pharmacol 2001; 60: 290-301.
51. Giannakakou P, Nakano Michel, Nicolaou KC, O'Brate A, Yu J, Blagosklonny MV, et al. Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics. Proc Natl Acad Sci USA 2002; 99: 10855-10860.
52. Bröker LE, Huisman C, Ferreira CG, Rodriguez JA, Kruyt FAE, Giaccone G. Late activation of apoptotic pathways plays a negligible role in mediating the cytotoxic effects of discodermolide and epothilone B in non-small cell lung cancer cells. Cancer Res 2002; 62:4081-4088.
53. Bröker LE, Huisman C, Span SW, Rodriguez JA, Kruyt FAE, Giaccone G. Cathepsin B Mediates Caspase-Independent Cell Death Induced by Microtubule Stabilizing Agents in Non-Small Cell Lung Cancer Cells. Cancer Res 2004; 64: 27-30.
54. Giannakakou P, Gussio R, Nogales E, Downing KH, Zaharevitz D, Bollbuck B, et al. A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells. Proc Natl Acad Sci USA 2000; 97: 2904-2909.
55. Nogales E, Wolf SG, Downing KH. Structure of the αβ tubulin dimer by electron crystallography. Nature 1998; 391: 199-203.
56. He L, Yang C-P, Horwitz SB. Mutations in β-tubulin map to domains involved in regulation of microtubule stability in epothilone-resistant cell lines. Molecular Cancer Ther 2001; 1: 3-10.
57. Verrills NM, Flemming CL, Liu M, Ivery MT, Cobon GS, Norris MD, et al. Microtubule alterations and mutations induced by desoxyepothilone B: Implications for Drug-Target Interactions. Chem Biol 2003; 10: 597-607.
58. Cabral F, Barlow SB. Resistance to antimitotic agents as genetic probes of microtubule structure and function. Pharmacol Ther 1991; 52: 159-171.
59. Poruchynsky MS, Giannakakou P, Ward Y, Bulinski JC, Telford WG, Robey RW et al. Accompanying protein alterations in malignant cells with a microtubule-polymerizing drug-resistance phenotype and a primary resistance mechanism. Biochem Pharmacol 2001; 62: 1469-1480.
60. Su DS, Balog A, Meng D, Bertinato P, Danishefsky SJ, Zheng YH, et al. Structure-activity relationships of the epothilones and the first in vivo comparison with paclitaxel. Angew Chem Int Ed Engl 1997; 36: 2093-2096.
61. Chou TC, Zhang XG, Balog A, Su DS, Meng D, Savin K, et al. Desoxyepothilone B: an efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone B. Proc Natl Acad Sci USA 1998; 95: 9642-9647.
62. Rothermel J, Wartmann M, Chen T, Hohneker T. EPO906 (epothilone B): a promising novel microtubule stabilizer. Seminars in Oncology 2003; 30, (Suppl 6): 51-55
63. Pietras K, Stumm M, Hubert M, Buchdunger E, Rubin K, Heldin C-K, et al. STI571 enhances the therapeutic index of epothilone B by a tumor-selective increase of drug uptake. Clinical Cancer Res 2003; 9: 3779-3787.
64. Sefkow M, Kiffe M, Schummer D, Höfle G. Oxidative and reductive transformations of epothilone A. Bioorg Med Chem Lett 1998; 8: 3025-3030.
65. Sefkow M, Kiffe M, Höfle G. Derivatization of the C12-C13 functional groups of epothilones A, B and C. Bioorg Med Chem Lett 1998; 8: 3031-3036.
66. Vite GD, Borzilleri RM, Kim SH, Regueiro-Rin A, Humphreys WG, Lee FYF. Epothilones A and B: Springboards for semisynthesis of promising antimitotic agents. In Ojima I, Vite GD, Altmann K-H Eds, Anticancer Agents-Frontiers in Cancer Chemotherapy. ACS Symposium Series 796. Washington DC, 2001, American Chemical Society 2001;148-170.
67. Meng D, Su DS, Balog A, Bertinato P, Sorensen EJ, Danishefsky SJ, et al. An Application to the Synthesis of Fully Active Epothilone Congeners. J Am Chem Soc 1997; 119: 2733-2734.
68. Su DS, Meng D, Bertinato P, Balog A, Sorensen EJ, Danishefsky SJ, et al. Total synthesis of (-)-epothilone B: an extension of the Suzuki coupling method and insights into structure-activity relationships of the epothilones. Angew Chem Int Ed Engl 1997; 36: 757-759.
69. Su DS, Balog A, Meng D, Bertinato P, Danishefsky SJ, Zheng YH, et al. Remote Effects in Macrolide Formation through Ring-Forming Olefin Metathesis: An Application to the Synthesis of Fully Active Epothilone Congeners. Angew Chem Int Ed Engl 1997; 36: 2093-2096.
70. Nicolaou KC, Winssinger N, Pastor J, Ninkovic S, Sarabia F, He Y, et al. Synthesis of epothilones A and B in solid and solution phase. Nature 1997; 387: 268-272.
71. Nicolaou KC, Vourloumis D, Li T, Pastor J, Winssinger N, He Y, et al. Designed epothilones: combinatorial synthesis, tubulin assembly properties, and cytotoxic action against taxol-resistant tumor cells. Angew Chem Int Ed Engl 1997; 36: 2097-2103.
72. Johnson J, Kim SH, Bifano M, DiMarco J, Fairchild C, Gougoutas J, et al. Synthesis, Structure Proof, and Biological Activity of Epothilone Cyclopropanes. Org Lett 2000; 2: 1537-1540.
73. Nicolaou KC, Namoto K, Li J, Ritzen A, Ulven T, Shoji M, et al. Chemical Synthesis and Biological Evaluation of cis- and trans-12,13-Cyclopropyl and 12,13-Cyclobutyl Epothilones and Related Pyridine Side Chain Analogues. Chem Bio Chem 2001; 2: 69-75.
74. Nicolaou KC, Namoto K, Ritzen A, Ulven T, Shoji M, Li J, et al. Total synthesis of epothilone B. J Am Chem Soc 2001; 123: 9313-9323.
75. Regueiro-Ren A, Borzilleri RM, Zheng X, Kim SH, Johnson JA, Fairchild, CR, et al. Synthesis and Biological Activity of Novel Epothilone Aziridines. Org Lett 2001; 3: 2693-2696.
76. Nicolaou KC, Ninkovic S, Finlay MR, Sarabia F, Li T, Total synthesis of 26-hydroxyepothilone B and related analogs. JCS Chem Commun 1997; 2343-2344.
77. Chappell MD, Harris CR, Kuduk SD, Balog A, Wu Z, Zhang F, et al. Probing the SAR of dEpoB via Chemical Synthesis: A Total Synthesis Evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B. J Org Chem 2002; 67: 7730-7736.
78. Newman RA, Yang J, Finlay MRV, Cabral F, Vourloumis D, Stevens LC, et al. Antitumor efficacy of 26-fluoroepothilone B against human prostate cancer xenografts. Cancer Chemother Pharmacol 2001; 48: 319-326.
79. Altmann K-H, Nicolaou KC, Wartmann M, O'Reilly, T. Proceedings of the American Association for Cancer Research 2001; 42: Abstract # 1979.
80. Altmann K-H, Bold G, Caravatti G, Denni D, Flörsheimer A, Schmidt A, et al. The total synthesis and biological assessment of trans-epothilone A. Helv Chim Acta 2002; 85:4086-4110.
81. Nicolaou KC, Ritzen A, Namoto K, Ruben MB, Diaz F, Andreu JM, et al. Chemical synthesis and biological evaluation of novel epothilone Band trans-12, 13-cyclopropyl epothilone B analogues. Tetrahedron 2002; 58: 6413-6432.
82. Nicolaou KC, Sarabia F, Ninkovic S, Finlay MR, Boddy CNC. Probing the ring size of epothilones: total synthesis of [14]-, [15]-, [17]-, and [18]Epothilones A. Angew Chem Int Ed Engl 1998; 37: 81-84.
83. Klar U, Skuballa W, Buchmann B, Schwede W, Bunte T, Hoffmann J, et al. Synthesis and biological activity of epothilones. In Ojima I, Vite GD, Altmann K-H Eds, Anticancer Agents-Frontiers in Cancer Chemotherapy. ACS Symposium Series 796. Washington DC, 2001; American Chemical Society 2001; 131-147.
84. Arslanian RL, Tang L, Blough S, Ma W, Qiu R-G, Katz L, et al. A new cytotoxic epothilone from modified polyketide synthases heterologously expressed in Myxococcus xanthus. J Nat Prod 2002; 65: 1061-1064.
85. Biswas K, Lin H, Njardson JT, Chappell MD, Chou T-C, Guan Y, et al. Highly Concise Routes to Epothilones: The Total Synthesis and Evaluation of Epothilone 490. J Am Chem Soc 2002; 124: 9825-9832.
86. Rivkin A, Njardson JT, Biswas K, Chou T-C, Danishefsky SJ. 4Total Syntheses of [17]- and [18]Dehydrodesoxyepothilones B via a Concise Ring-Closing Metathesis-Based Strategy: Correlation of Ring Size with Biological Activity in the Epothilone Series. J Org Chem 2002; 67: 7737-7740.
87. Rivkin A, Biswas K, Chou T-C, Danishefsky SJ. On the Introduction of a Trifluoromethyl Substituent in the Epothilone Setting: Chemical Issues Related to Ring Forming Olefin Metathesis and Earliest Biological Findings. Org Lett 2002; 4: 4081-4084.
88. Rivkin A, Yoshimura F, Gabarda AE, Chou T-C, Dong H, Tong WP, et al. Complex Target-Oriented Total Synthesis in the Drug Discovery Process: The Discovery of a Highly Promising Family of Second Generation Epothilones. J Am Chem Soc 2003; 125: 2899-2901.
89. Yoshimura F, Rivkin A, Gabarda AE, Chou T-C, Dong H, Sukenick G, et al. Synthesis and conformational analysis of (E)-9, 10-dehydroepothilone B: A suggestive link between the chemistry and biology of epothilones. Angew Chem Int Ed 2003; 42:2518-2521.
90. Chou T-C, Dong H, Rivkin A, Yoshimura F, Gabarda AE, Cho YS, et al. Design and total synthesis of a superior family of epothilone analogues, which eliminate xenograft tumors to a nonrelapsable state. Angew Chem Int Ed 2003; 42: 4762-4767.
91. Tang L, Li R-G, Yong L, Katz LJ. Generation of novel epothilone analogs with cytotoxic activity by biotransformation. Antibiotics 2003; 56: 16-23.
92. Starks CM, Zhou Y, Liu F, Licari P. Isolation and Characterization of New Epothilone Analogues from Recombinant Myxococcus xanthus Fermentations. J Nat Prod 2003; 66:1313-1317.
93. (a) White JD, Carter RG, Sundermann KF, Wartmann M. Total Synthesis of Epothilone B, Epothilone D, and cis- and trans-9,10-Dehydroepothilone D. J Am Chem Soc 2001; 123: 5407-5413.
94. (b) White JD, Carter RG, Sundermann KF, Wartmann M. Total Synthesis of Epothilone B, Epothilone D, and cis- and trans-9,10-Dehydroepothilone D Erratum for J Am Chem Soc 2001; 123, 5407-5413. J Am Chem Soc 2003; 125: 3190.
95. Chou TC, Zhang XG, Harris CR, Kuduk SD, Balog A, Savin KA, et al. Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel. Proc Natl Acad Sci USA 1998, 95: 15798-15802.
96. Carlomagno T, Blommers MJJ, Meiler J, Jahnke W, Schupp T, Petersen F, et al. The high-resolution solution structure of epothilone a bound to tubulin: An understanding of the structure-activity relationships for a powerful class of antitumor agents. Angew Chem Int Ed 2003; 42:2511-2515.
97. Qintard D, Bertrand P, Vielle S, Raimbaud E, Renard P, Pfeiffer B, et al. Enantioselective synthesis of 2, 3-dehydro-3-desoxy-10-oxa epothilone D. Synlett 2003; 13: 2033-2036.
98. Klar U, Schwede W, Skuballa W, Buchmann B, Hoffmann J, Lichtner R. 6-Alkenyl, 6-alkynyl-, and 6-epoxy-epothilone derivatives, process for their production and their use in pharmaceutical preparations. PCT Int Appl 2002; WO 0066589.
99. Borzilleri RM, Zheng X, Schmidt RJ, Johnson JA, Kim SH, DiMarco JD, et al. A Novel Application of a Pd(0)-Catalyzed Nucleophilic Substitution Reaction to the Regio- and Stereoselective Synthesis of Lactam Analogues of the Epothilone Natural Products. J Am Chem Soc 2000; 122: 8890-8897.
100. Lee FY, Borzilleri R, Fairchild CR, Kim SH, Long BH, Reventos-Suarez C, et al. BMS-247550: A novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin Cancer Res 2001; 7: 1429-1437.
101. Höfle G, Glaser N, Kiffe M, Hecht H-J, Sasse F, Reichenbach H. N-oxidation of epothilone A-C and O-acyl rearrangement to C-19- and C21-substituted epothilones. Angew Chem Int Ed Engl 1999; 38: 1971-1974.
102. Sefkow M, Höfle G. Substitutions at the thiazole moiety of epothilone. Heterocycles 1998; 48: 2485-2488.
103. Nicolaou KC, King NP, Finlay MRV, He Y, Roschangar F, Vourloumis D, et al. Total synthesis of epothilone E and related side-chain modified analogues via a Stille coupling based strategy. Bioorg Med Chem 1999; 7: 665-697.
104. Nicolaou KC, Scarpelli R, Bollbuck B, Werschkun B, Pereira MM, Wartmann M, et al. Chemical synthesis and biological properties of pyridine epothilones. Chem Biol 2000; 7: 593-599.
105. Nicolaou KC, Hepworth D, King NP, Finlay MR, Scarpelli R, Pereira MM, et al. Total synthesis of 16-desmethylepothilone B, epothilone B10, epothilone F, and related side chain modified epothilone B analogues. Chem Eur J 2000; 6: 2783-2800.
106. Nicolaou KC, Hepworth D, Finlay MRV, Paul KN, Werschkun B, Bigot A. Synthesis of 16-Desmethylepothilone B: improved methodology for the rapid highly selective and convergent construction of epothilone B and analogues. JCS Chem Comm 1999; 519-520.
107. Altmann K-H, Blommers MJJ, Caravatti G, Flörsheimer A, Nicolaou KC, O'Reilly T, et al. Synthetic and semisynthetic analogs of epothilones: chemistry and biological activity. In Ojima I, Vite GD, Altmann K-H Eds, Anticancer Agents-Frontiers in Cancer Chemotherapy. ACS Symposium Series 796. Washington DC, 2001, American Chemical Society 2001; 112-130.
108. Altmann K-H, Bold G, Caravatti G, Flörsheimer A, Guagnano V, Wartmann, M. Synthesis and biological evaluation of highly potent analogues of epothilones Band D. Bioorg. Med. Chem. Lett. 2000; 10: 2765-2768.
109. Wartmann M, Loretan J, Reuter R, Hattenberger M, Muller M, Vaxelaire J, et al. Preclinical pharmacological profile of ABJ879, a novel epothilone B analog with potent and protracted anti-tumor activity. Proceedings of the American Association for Cancer Research 2004; 45: Abstract #5440.
110. Nicolaou KC, Sasmal PK, Rassias G, Reddy MV, Altmann K-H, Wartmann M, et al. Design, synthesis, and biological properties of highly potent epothilone B analogues. Angew Chem Int Ed 2003: 42:3515-3520.
111. Ojima I, Chakravarty S, Inoue T, Lin S, He L, Horwitz SB, et al. A common pharmacophore for cytotoxic natural products that stabilize microtubules. Proc Natl Acad Sci USA 1999; 96: 4256-4261.
112. Wang M, Xia X, Kim Y, Hwang D, Jansen JM, Botta M, et al. A Unified and Quantitative Receptor Model for the Microtubule Binding of Paclitaxel and Epothilone: Org Lett 1999; 1: 43-46.
113. Manetti F, Forli S, Maccari L, Corelli F, Botta M. 3D QSAR studies of the interaction between β-tubulin and microtubule stabilizing antimitotic agents (MSAA). A combined pharmacophore generation and pseudoreceptor modeling approach applied to taxanes and epothilones. II Farmaco 2003; 58: 357-361.
114. Manetti F, Maccari L, Corelli F, Botta M. 3D QSAR models of interactions between β-tubulin and microtubule stabilizing antimitotic agents (MSAA): A survey on taxanes and epothilones. Curr Topics Med Chem 2004; 4: 203-217.
115. Taylor RE, Chen Y, Beatty A, Myles DC, Zhou Y. Conformation-Activity Relationships in Polyketide Natural Products: A New Perspective on the Rational Design of Epothilone Analogues. J Am Chem Soc 2003; 125: 26-27.
116. Taylor RE, Chen Y, Galvin GM, Pabba PK. Conformation-activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone. Org Biomol Chem 2004; 2: 127-132.
117. Chou TC, O'Connor OA, Tong WP, Guan Y, Zhang ZG, Stachel S J, et al. The synthesis, discovery, and development of a highly promising class of microtubule stabilization agents: curative effects of desoxyepothilones B and F against human tumor xenografts in nude mice. Proc Natl Acad Sci USA 2001; 98:8113-8118.
118. Stachel SJ, Lee CB, Spassova M, Chappell MD, Bornmann WG, Danishefsky SJ, et al. On the Interactivity of Complex Synthesis and Tumor Pharmacology in the Drug Discovery Process: Total Synthesis and Comparative in vivo Evaluation of the 15-Aza Epothilones. J Org Chem 2001; 66:4369-4378.
119. Lee CB, Chou TC, Zhang XG, Wang ZG, Kuduk SD, Chappell MD, et al. Total Synthesis and Antitumor Activity of 12, 13-Desoxyepothilone F: An Unexpected Solvolysis Problem at C15, Mediated by Remote Substitution at C21. J Org Chem 2000; 65: 6525-6533.
120. Yamaguchi H, Paranawithana SR, Lee MW, Huang Z, Bhalla KN, Wang HG. Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells. Cancer Research 2002; 62: 466-471.
121. Griffin D, Wittmann S, Guo F, Nimmanapalli R, Bali P, Wang HG. et al. Molecular determinants of epothilone B derivative (BMS 247550) and Apo-2L/TRAIL-induced apoptosis of human ovarian cancer cells. Gynecologic Oncology 2003; 89: 37-47.
122. Guo F, Nimmanapalli R, Paranawithana S, Wittman S, Griffin D, Bali P, et al. Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothiloue B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis. Blood 2002; 99: 3419-3426.
123. Kim J-C, Kim J-S, Saha D, Cao Q, Shyr Y, Choy Hak. Potential radiation-sensitizing effect of semisynthetic epothilone B in human lung cancer cells. Radiotherapy and Oncology 2003; 68:305-313.
124. Lin N, Brakora K, Seiden M. BMS-247550(Bristol-Myers Squibb/GBF). Curr Opin Investigational Drugs; 2003; 4: 746-756.
125. Agrawal M, Edgerly M, Fojo T, Kotz H. Treatment of recurrent cervical adenocarcinoma with BMS-247550, an epothilone B analog. Gynecologic Oncology 2003; 90: 96-99.
126. Mani S, McDaid H, Hamilton A, Hochster H, Cohen MB, Khabelle D, et al. Phase I Clinical and Pharmacokinetic Study of BMS-247550, a Novel Derivative of Epothilone B, in Solid Tumors. Clin Canc Res 2004; 10: 1289-1298.
127. McDaid HM, Mani S, Shen H-J, Muggia F, Sonnichsen D, Horwitz SB. Validation of the pharmacodynamics of BMS-247550, an analogue of epothilone B, during a phase I clinical study. Clin Canc Res 2002; 8: 2035-2043.
128. Vite G, Höfle G, Bifano M, Fairchild C, Glaser N, Johnston K, et al. The semisynthesis and preclinical evaluation of BMS-310705, an epothilone analog in clinical development. Abstracts of Papers, 223rd ACS National Meeting, Orlando, FL, United States, April 7-11, 2002, MEDI-018.
129. Höfle G, Glaser N, Leibold T. Synthesis and cytotoxicity of C-21 modified epothilones. Ger Offen 2000; DE 19907588 Al 20000824.
130. Uyar D, Takigawa N, Mekhail T, Grabowski D, Markman M, Lee F, et al. Apoptotic pathways of epothilone BMS 310705. Gynecologic Oncology 2003; 91: 173-178.
131. Spriggs D, Dupont J, Pezzulli S, Larkin J, Cropp J, Johnson R, et al. Phase 1 dose escalating and pharmacokinetic (PK) study of KOS-862 (epothilone D): Phase 2 dose and schedule defined. AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, Nov 17-21, 2003, Boston, MA, USA, Abstract-# A248. Published as a Supplement to Clinical Cancer Research, Volume 9, Issue 16 (Dec 1, 2003).
132. Holen K, Hannah A, Zhou Y, Cropp G, Johnson R, Volkman J, Binger K, et al. A phase I study to determine the safety and pharmacokinetics of continuous intravenous administration of KOS-862 (Epothilone D) in patients with solid tumors. AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, Nov 17-21, 2003, Boston, MA, USA. Abstract-# A261. Published as a Supplement to Clinical Cancer Research, Volume 9, Issue 16 (Dec 1, 2003).
133. Garraway LA, Chabner B. MDR1 inhibition: less resistance or less relevance? Eur J Cancer 2002; 38: 2337-2340.
134. Altaha R, Fojo T, Reed E, Abraham J. Epothilones: a novel class of non-taxane microtubule-stabilizing agents. Curr Pharm Design 2002; 8(19): 1707-12.
135. Hamann MT. Enhancing marine natural product structural diversity and bioactivity through semisynthesis and biocatalysis. Curr Pharm Design 2003; 9(11): 879-89.
136. Searcey M. Duocarmycins - natures prodrugs? Curr Pharm Design 2002; 8(15): 1375-89.