The epothilones and related analogues - A review of their syntheses and anti-cancer activities

Current Pharmaceutical Design

Volumn 11, Issue 13, 2005, Pages 1615-1653

  Watkins, E Blake ^a   Chittiboyina, Amar G ^a   Jung, Jae Chul ^a   Avery, Mitchell A ^a  

^a UNIVERSITY OF MISSISSIPPI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; DESOXYEPOTHILONE F; DOCETAXEL; EPOTHILONE A; EPOTHILONE B; EPOTHILONE C; EPOTHILONE D; EPOTHILONE DERIVATIVE; PACLITAXEL; UNCLASSIFIED DRUG; VINBLASTINE;

ALDOL REACTION; ANTINEOPLASTIC ACTIVITY; CANCER CELL CULTURE; CHEMICAL INTERACTION; CHEMICAL REACTION; CYTOTOXICITY; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOSELECTIVITY; HUMAN; HYDROBORATION; IN VITRO STUDY; OLEFINATION; PRIORITY JOURNAL; REVIEW; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANIMALS; ANTINEOPLASTIC AGENTS; EPOTHILONES; HUMANS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 18744410664     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/1381612053764742     Document Type: Review

References (115)

1. von Angerer E. Tubulin as a target for anticancer drugs. Curr Op Drug Disc Dev 2000; 3: 575.
2. Altmann KH. Microtubule-stabilizing agents: a growing class of important anticancer drugs. Curr Op Chem Biol 2001; 5: 424.
3. Correia JJ, Lobert S. Physiochemical aspects of tubulin-interacting antimitotic drugs. Curr Pharm Design 2001; 7: 1213.
4. He L, Orr GA, Horwitz SB. Novel molecules that interact with microtubules and have functional activity similar to Taxol. Drug Disc Today 2001; 6: 1153.
5. Kavallaris M, Verrills NM, Hill BT. Anticancer therapy with novel tubulin-interacting drugs. Drug Resistance Updates 2001; 4: 392.
6. Jordan MA. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem Anti-Cancer Agents 2002; 2: 1.
7. Wood KW, Cornwell WD, Jackson JR. Past and future of the mitotic spindle as an oncology target. Curr Op Pharm 2001; 1: 370.
8. Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumor agents VI. The isolation and structure of taxol, a novel antileukemic and antitumour agent from taxus brevifolia. J Am Chem Soc 1971; 93: 2325.
9. Schiff PB, Fant J, Horwitz Susan B. Promotion of microtubule assembly n vitro by taxol. Nature 1979; 277: 665.
10. Palmer CG, Livengood D, Warren AK, Simpson PJ, Johnson IS. The action of vincaleukoblastine on mitosis in vitro. Exp Cell Res 1960; 20: 198.
11. Gerth K, Bedorf N, Hofle G, Irschik H, Reichenbach H. Antibiotics from gliding bacteria. 74. Epothilons A and B: antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria): production, physico-chemical and biological properties. J Antibiot 1996; 49: 560.
12. Hofle G, Bedorf N, Steinmetz H, Schomburg D, Gerth K, Reichenbach H. Antibiotics from gliding bacteria. 77. Epothilones A and B - novel 16-membered macrolides with cytotoxic activity: isolation, crystal structure, and conformation in solution. Angew Chem Int Ed Eng 1996; 35: 1567.
13. Hofle G, Bedorf N, Gerth K, Reichenbach H. Chem Abstr 1993; 120: 52841.
14. 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 Research 1995; 55: 2325.
15. Dorr RT. Pharmacology and toxicology of Cremophor EL diluent. Ann Pharmacother 1994; 28: S11.
16. Vau Oosterom AT. Docetaxel (Taxotere): an effective agent in the management of second-line breast cancer. Semin Oncol 1995; 22: 22.
17. Rowinsky EK. The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Annu Rev Med 1997; 48: 353.
18. 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.
19. Sackett DL, Giannakakou P, Poruchynsky MS, Fojo A. Tubulin from paclitaxel-resistant cells as a probe for novel antimicrotubule agents. Cancer Chemother Pharmacol 1997; 40: 228.
20. Nicolaou KC, Roschangar F, Vourloumis D. Chemical biology of epothilones. Angew Chem Int Ed Eng 1998; 37: 2014.
21. 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.
22. Mulzer J, Martin HJ, Berger M. Progress in the synthesis of chiral heterocyclic natural products: epothilone B and tartrolon BJ. Heterocycl Chem 1999; 36: 1421.
23. Mulzer J. Epothilone B and its derivatives as novel antitumor drugs: total and partial synthesis and biological evaluation. Monatsh Chem 2000; 131: 205.
24. Nicolaou KC, Ritzen A, Namoto K. Recent developments in the Chemistry biology and medicine of the epothilones. Chemical Communications (Cambridge, United Kingdom), 2001; 1523-1535.
25. Zhang R, Liu Z. Recent Progress in the Synthesis of Epothilones. Curr Org Chem 2004; 8: 267.
26. Hindupur RM, Panicker B, Valluri M, Avery MA. Total synthesis of epothilone A. Tetrahedron Lett 2001; 42: 7341.
27. Panicker B, Karle JM, Avery MA. An unusual reversal of stereoselectivity in a boron mediated aldol reaction: enantioselective synthesis of the C1-C6 segment of the epothilones. Tetrahedron 2000; 56: 7859.
28. Valluri M, Hindupur RM, Bijoy P, Labadie G, Jung J-C, Avery MA. Total synthesis of epothilone B. Org Lett 2001; 3: 3607.
29. Zheng Y, Avery MA. Asymmetric aldol reactions using catalytic D-(+)-proline: a new, economic and practical approach to a commonly employed C1-C6 keto-acid synthon of the epothilones. Tetrahedron 2004; 60: 2091.
30. Balog A, Meng DF, Kamenecka T, Bertinato P, Su DS, Sorensen EJ, et al. Total synthesis of (-)-epothilone A. Angew. Chem Int Engl 1996; 35: 2801.
31. Su DS, Meng D, Bertinato P, Balog A, Sorensen EJ, Danishefsky SJ, et al. Structure-activity relationships of the epothilones and the first in vivo comparison with paclitaxel. Angew. Chem Int Engl 1997; 36: 757.
32. Meng DF, Bertinato P, Balog A, Su DS, Kamenecka T, Sorensen EJ, et al. Total syntheses of epothilones A and B. J Am Chem Soc 1997; 119: 10073.
33. Balog A, Harris CR, Savin K, Zhang XG, Chou TC, Danishefsky SJ. A novel aldol condensation with 2-methyl-4-pentenal and its application to an improved total synthesis of epothilone B. Angew Chem Int Engl 1998, 37: 2675.
34. Bertinato P, Sorensen EJ, Meng D, Danishefsky SJ. Studies toward a synthesis of epothilone A: stereocontrolled assembly of the acyl region and models for macrocyclization. J Org Chem 1996; 61: 8000.
35. Lee CB, Wu Z, Zhang F, Chappell MD, Stachel SJ, Chou T-C, et al. Insights into long-range structural effects on the stereochemistry of aldol condensations: a practical total synthesis of desoxyepothilone F. J Am Chem Soc 2001; 123: 5249.
36. 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.
37. Martin HJ, Dreshcer M, Mulzer J. How stable are epoxides? A novel synthesis of epothilone B. Angew. Chem Int Engl 2000; 39: 581.
38. Martin HJ, Pojarliev P, Kahlig H, Mulzer J. The 12,13-diol cyclization approach for a truly stereocontrolled total synthesis of epothilone B and the synthesis of a conformationally restrained analog. Chem - Eur J 2001; 7: 2261.
39. Taylor RE, Chen Y. Total synthesis of epothilones Band D. Org Lett 2001; 3: 2221.
40. Martin N, Thomas EJ. Total syntheses of epothilones B and D: applications of allylstannanes in organic synthesis. Tetrahedron Lett 2001; 42: 8373.
41. Sun J, Sinha SC. Stereoselective total synthesis of epothilones by the metathesis approach involving C9-C10 bond formation. Angew Chem Int Ed Eng 2002; 41: 1381.
42. Scholl M, Ding S, Lee CW, Grubbs RH. Synthesis and activity of a new generation of ruthenium-based olefin metathesis catalysts coordinated with 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligands. Org Lett 1999; 1: 953.
43. Ermolenko MS, Potier P. Synthesis of epothilones B and D from D-glucose. Tetrahedron Lett 2002; 43: 2895.
44. Kolb HC, Sharpless BA simplified procedure for the stereospecific transformation of 1,2-diols into epoxides. Tetrahedron 1992; 48: 10515.
45. Liu Z-Y, Chen Z-C, Yu C-Z, Wang R-F, Zhang R-Z, Huang C-S, et al. Total synthesis of epothilone A through stereospecific epoxidation of the p-methoxybenzyl ether of epothilone C. Chem - Eur J 2002; 8: 3747.
46. Liu J, Wong C-H. Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem Int Ed Eng 2002; 41: 1404.
47. Storer RI, Takemoto T, Jackson PS, Ley SV. A total synthesis of epothilones using solid-supported reagents and scavengers. Angew Chem Int Ed Eng 2003; 42: 2521.
48. Koch G, Loiseleur O, Fuentes D, Jantsch A, Altmann K-H. Diastereoselective titanium enolate aldol reaction for the total synthesis of epothilones. Org Lett 2002; 4: 3811.
49. Chandrasekhar S, Reddy CR. Towards a synthesis of epothilone A: asymmetric synthesis of C(1)-C(6) and C(7)-C(15) fragments. Tetrahedron: Asymmetry 2002; 13: 261.
50. Ramachandran PV, Prabhudas B, Pratihar D, Chandra JS, Reddy MVR. Stereoselective synthesis of the C7-C21 segment of epothilone A via asymmetric alkoxyallyl- and crotylboration. Tetrahedron Lett 2003; 44: 3745.
51. Shioji K, Kawaoka H, Miura A, Okuma K. Synthesis of C1-C6 fragment for epothilone A via lipase-catalyzed optical resolution. Syn. Commun 2001; 31: 3569.
52. 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.
53. Stachel SJ, Danishefsky SJ. Chemo- and stereoselective epoxidation of 12,13-desoxyepothilone B using 2,2′-dimethyldioxirane. Tetrahedron Lett 2001; 42: 6785.
54. Biswas K, Lin H, Njardarson 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.
55. Yamamoto K, Biswas K, Gaul C, Danishefsky SJ. Effects of temperature and concentration in some ring closing metathesis reactions. Tetrahedron Lett 2003; 44: 3297.
56. Njardarson JT, Biswas K, Danishefsky SJ. Application of hitherto unexplored macrocyclization strategies in the epothilone series: novel epothilone analogs by total synthesis. Chem Commun 2002; 2759.
57. Rivkin A, Njardarson JT, Biswas K, Chou T-C, Danishefsky SJ. Total 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. Journal of Organic Chemistry 2002; 67: 7737-7740.
58. 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.
59. 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.
60. 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.
61. 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 Eng 2003; 42: 2518.
62. Rivkin A, Cho YS, Gabarda AE, Yoshimura F, Danishefsky SJ. Application of ring-closing metathesis reactions in the synthesis of epothilones. J Nat Prod 2004; 67: 139.
63. Nicolaou KC, Namoto K, Li J, Ritzen A, Ulven T, Shoji M, et al. Synthesis and biological evaluation of 12,13-cyclopropyl and 12,13-cyclobutyl epothilones. Chem BioChem 2001; 2: 69.
64. 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 Eng 2003; 42: 3515
65. Nicolaou KC, Ritzen A, Namoto K, Buey RM, Diaz JF, Andreu JM, et al. Chemical synthesis and biological evaluation of novel epothilone B and trans-12,13-cyclopropyl epothilone B analogues Tetrahedron 2002; 58: 6413-6432.
66. 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.
67. White JD, Sundermann KF, Wartmann M. Synthesis Conformational Analysis, and Bioassay of 9,10-Didehydroepothilone D. Org Lett 2002; 4: 995.
68. Hofle G, Glaser N, Kiffe M, Hecht HJ, Sasse F, Reichenbach H. N-oxidation of epothilone A-C and O-acyl rearrangement to C-19-and C-21-substituted epothilones. Angew. Chem Int Engl 1999; 38: 1971.
69. Borzilleri RM, Vite GD. Epothilones: new tubulin polymerization agents in preclinical and clinical development. Drugs of the Future 2002; 27: 1149.
70. Hofle G, Glaser N, Leibold T, Karama U, Sasse F, Steinmetz H. Semisynthesis and degradation of the tubulin inhibitors epothilone and tubulysin. Pure and Applied Chemistry 2003; 75: 167.
71. Nicolaou KC, Hepworth D, King NP, Raymond M, Finlay V, Scarpelli R, 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.
72. Karama U, Hofle G. Synthesis of epothilone 16,17-alkyne analogs by replacement of the C13-C15(O)-ring segment of natural epothilone C. Eur J Org Chem 2003; 1042.
73. Regueiro-Ren A, Borzilleri RM, Zheng X, Kim S-H, Johnson JA, Fairchild CR, et al. Synthesis and biological activity of novel epothilone aziridines. Org Lett 2001; 3: 2693.
74. Regueiro-Ren A, Leavitt K, Kim S-H, Hoefle G, Kiffe M, Gougoutas JZ, et al. SAR and pH stability of cyano-substituted epothilones. Org Lett 2002; 4: 3815.
75. Altmann K-H, Bold G, Caravatti G, Denni D, Florsheimer A, Schmidt A, et al. The total synthesis and biological assessment of trans-epothilone A. Helv. Chim Acta 2002; 85: 4086.
76. Quintard 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; 2033.
77. Ganesh T, Schilling JK, Palakodety RK, Ravindra R, Shanker N, Bane S, et al. Synthesis and biological evaluation of fluorescently labeled epothilone analogs for tubulin binding studies. Tetrahedron 2003; 59, 9979.
78. Dong SD, Sundermann KF, Smith KMJ, Petryka J, Fenghua L, Myles DC. Rapid access to epothilone analogs via semisynthetic degradation and reconstruction of epothilone D. Tetrahedron Lett 2004; 45: 1945.
79. Gerth K, Steinmetz H, Hofle G, Reichenbach H. Studies on the biosynthesis of epothilones: hydroxylation of epo A and B to epothilones E and F. J Antibiot 2002; 55: 41.
80. 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.
81. Starks CM, Zhou Y, Liu F, Licari PJ. Isolation and characterization of new epothilone analogues from recombinant myxococcus xanthus fermentations. J Nat Prod 2003; 66: 1313.
82. Yamaguchi H, Paranawithana SR, Lee MW, Huang Z, Bhalla KN, Wang H-G. Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells. Cancer Res 2002; 62: 466.
83. Rothermel J, Wartmann M, Chen T, Hohneker J. EPO906 (epothilone B): a promising novel microtubule stabilizer. Sem Oncol 2003; 30: 51.
84. Agrawal NR, Ganapathi R, Mekhail T. Tubulin interacting agents: novel taxanes and epothilones. Curr Oncol Rep 2003; 5: 89.
85. Bocci G, Nicolaou KC, Kerbel RS. Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res 2002; 62: 6938.
86. 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.
87. 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.
88. Abraham J, Agrawal M, Bakke S, Rutt A, Edgerly M, Balis Frank M, et al. Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days. J Clin Oncol 2003; 21: 1866.
89. 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 Cancer Res 2002; 8: 2035.
90. Chou T-C, O'Connor OA, Tong WP, Guan Y, Zhang Z-G, Stachel SJ, 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. Proceedings of the National Academy of Sciences USA 2001; 98: 8113.
91. Tang L, Qiu R-G, Li Y, Katz L. Generation of novel epothilone analogs with cytotoxic activity by biotransformation. J Antibiot 2003; 56: 16.
92. 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 Eng 2003; 42: 2511.
93. 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-.
94. 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 2003; 2: 127.
95. 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. Farmaco 2003; 58: 357.
96. Buey RM, Diaz JF, Andreu JM, O'Brate A, Giannakakou P, Nicolaou KC, et al. Interaction of epothilone analogs with the paclitaxel binding site relationship between binding affinity, microtubule stabilization, and cytotoxicity. Chem Biol 2004; 11: 225.
97. Altmann K-H. Epothilone B and its analogs - a new family of anticancer agents. Mini-Reviews in Medicinal Chemistry 2003; 3: 149.
98. Wartmann M, Altmann KH. The biology and medicinal chemistry of epothilones. Curr Med Chem Anti-Cancer Agents 2002; 2: 123.
99. Tang L, Shah S, Chung L, Carney J, Katz L, Khosla C, et al. Cloning and heterologous expression of the epothilone gene cluster. Science 2000; 287: 640.
100. Molnar I, Schupp T, Ono M, Zirkle RE, Milnamow M, Nowak-Thompson B, et al. The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90. Chem Biol 2000; 7: 97.
101. Julien B, Shah S, Chung L, Ziermann R, Goldman R, Katz L, et al. Isolation and characterization of the epothilone biosynthetic gene cluster from Sorangium cellulosum. Gene 2000; 249: 153.
102. Walsh CT, O'Connor SE, Schneider TL. Polyketide-nonribosomal peptide epothilone antitumor agents: the EpoA, B, C subunits. J Ind Microbiol Biotech 2003; 30: 448.
103. O'Connor SE, Chen H, Walsh CT. Enzymatic assembly of epothilones: the EpoC subunit and reconstitution of the EpoA-ACP/B/C polyketide and nonribosomal peptide interfaces. BioChemistry 2002; 41: 5685.
104. Chen H, O'Connor S, Cane DE, Walsh CT. Epothilone biosynthesis: assembly of the methylthiazolylcarboxy starter unit on the EpoB subunit. Chem Biol 2001; 8: 899.
105. Boddy CN, Schneider TL, Hotta K, Walsh CT, Khosla C. Epothilone C macrolactonization and hydrolysis are catalyzed by the isolated thioesterase domain of epothilone polyketide synthase. J Am Chem Soc 2003; 125: 3428.
106. Hardt IH, Steinmetz H, Gerth K, Sasse F, Reichenbach H, Hoefle 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.
107. O'Connor SE, Walsh CT, Liu F. Biosynthesis of epothilone intermediates with alternate starter units: Engineering polyketide-nonribosomal interfaces. Angew Chem Int Ed Eng 2003; 42: 3917.
108. Schneider TL, Walsh CT, O'Connor SE. Utilization of alternate substrates by the first three modules of the epothilone synthetase assembly line. J Am Chem Soc 2002; 124: 11272.
109. 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.
110. Julien B, Shah S. Heterologous expression of epothilone biosynthetic genes in Myxococcus xanthus. Antimicrob Agents Chemother 2002; 46: 2772.
111. Arslanian RL, Parker CD, Wang PK, McIntire JR, Lau J, Starks C, et al. Large-scale isolation and crystallization of epothilone D from Myxococcus xanthus cultures. J Nat Prod 2002; 65: 570.
112. Lau J, Frykman S, Regentin R, Ou S, Tsuruta H, Licari P. Optimizing the heterologous production of epothilone D in Myxococcus xanthus. Biotech Bioeng 2002; 78: 280.
113. 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.
114. Anderson WF, Umar A, Viner JL, Hawk ET. The role of cyclooxygenase inhibitors in cancer prevention. Curr Pharm Design 2002; 8(12): 1035-62.
115. Westphal EM, Melchner Hv H. Gene therapy approaches for the selective killing of cancer cells. Curr Pharm Design 2002; 8(19): 1683-94.