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Epothilone D

Description of Epothilone D: epothilone D is a natural polyketide compound isolated from the myxobacterium Sorangium cellulosum. Also known as desoxyepothilone B, epothilone D binds to tubulin and inhibits the disassembly of microtubules, resulting in the inhibition of mitosis, cellular proliferation, and cell motility. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:   Kosan.

The epothilones are a new class of cytotoxic molecules identified as potential chemotherapeutic drugs. As of September 2008[update], epothilones A to F have been identified and characterised. Early studies in cancer cell lines and in human cancer patients indicate superior efficacy to the taxanes. Their mechanism of action is similar, but their chemical structure is simpler. Due to their better water solubility, cremophors (solubilizing agents used for paclitaxel which can affect cardiac function and cause severe hypersensitivity) are not needed. Endotoxin-like properties known from paclitaxel, like activation of macrophages synthesizing inflammatory cytokines and nitric oxide, are not observed for epothilone B. Epothilones were originally identified as metabolites produced by the myxobacterium Sorangium cellulosum. see http://en.wikipedia.org/wiki/Epothilone.

Clinical trials about Epotilones:

 Several epothilone analogs are currently undergoing clinical development for treatment of various cancers. One analog, ixabepilone, was approved in October 2007 by the United States Food and Drug Administration for use in the treatment of aggressive metastatic or locally advanced breast cancer no longer responding to currently available chemotherapies.  In November 2008, the EMEA has refused a marketing authorisation for Ixabepilone.  Epothilone B has proven to contain potent in vivo anticancer activities at tolerate dose levels in several human xenograft models.  As a result, epothilone B and its various analogues are currently undergoing various clinical phases (patupilone [EPO906] and sagopilone [SH-Y03757A, ZK-EPO, chemical structure] are in phase II trials; BMS-310705 and BMS-247550 in phase I trials). Results of a phase III trial with ixabepilone in combination with capecitabine in metastatic breast cancer have been announced. see http://en.wikipedia.org/wiki/Epothilone.

  1: Chen QH, Ganesh T, Jiang Y, Banerjee A, Sharma S, Bane S, Snyder JP, Kingston DG. Novel epothilone lactones by an unusual diversion of the Grubbs' metathesis reaction. Chem Commun (Camb). 2010 Mar 28;46(12):2019-21. Epub 2010 Feb 9. PubMed PMID: 20221478.

2: Reiff EA, Nair SK, Henri JT, Greiner JF, Reddy BS, Chakrasali R, David SA, Chiu TL, Amin EA, Himes RH, Vander Velde DG, Georg GI. Total synthesis and evaluation of C26-hydroxyepothilone D derivatives for photoaffinity labeling of beta-tubulin. J Org Chem. 2010 Jan 1;75(1):86-94. PubMed PMID: 19954175; PubMed Central PMCID: PMC2798899.

3: Prantz K, Mulzer J. Synthesis of (Z)-trisubstituted olefins by decarboxylative grob-type fragmentations: epothilone D, discodermolide, and peloruside A. Chemistry. 2010 Jan 11;16(2):485-506. PubMed PMID: 19943284.

4: Zhang C, Zhao L, Qi W, Meng Z, Sun G, Dou G. Simultaneous determination of epothilone D and its hydrolytic metabolite in human plasma by high performance liquid chromatography-tandem mass spectrometry for pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Nov 1;877(29):3748-52. Epub 2009 Sep 6. PubMed PMID: 19775943.

5: Cheng KL, Bradley T, Budman DR. Novel microtubule-targeting agents - the epothilones. Biologics. 2008 Dec;2(4):789-811. PubMed PMID: 19707459; PubMed Central PMCID: PMC2727900.

6: Frein JD, Taylor RE, Sackett DL. New sources of chemical diversity inspired by biosynthesis: rational design of a potent epothilone analogue. Org Lett. 2009 Aug 6;11(15):3186-9. PubMed PMID: 19572566; PubMed Central PMCID: PMC2736359.

7: Prantz K, Mulzer J. Decarboxylative Grob-type fragmentations in the synthesis of trisubstituted Z olefins: application to peloruside A, discodermolide, and epothilone D. Angew Chem Int Ed Engl. 2009;48(27):5030-3. PubMed PMID: 19492384.

8: Chen QH, Ganesh T, Brodie P, Slebodnick C, Jiang Y, Banerjee A, Bane S, Snyder JP, Kingston DG. Design, synthesis and biological evaluation of bridged epothilone D analogues. Org Biomol Chem. 2008 Dec 21;6(24):4542-52. Epub 2008 Nov 6. PubMed PMID: 19039362; PubMed Central PMCID: PMC2790820.

9: Keck GE, Giles RL, Cee VJ, Wager CA, Yu T, Kraft MB. Total synthesis of epothilones B and D: stannane equivalents for beta-keto ester dianions. J Org Chem. 2008 Dec 19;73(24):9675-91. PubMed PMID: 18991385; PubMed Central PMCID: PMC2736362.

10: Zhang SQ, Vinnakota H, Jung JC, Carvalho P, Chittiboyina AG, Avery MA, Avery BA. Determination of a novel epothilone D analog (AV-EPO-106) in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry. Biomed Chromatogr. 2009 Mar;23(3):302-7. PubMed PMID: 18800336.

11: Park SR, Park JW, Jung WS, Han AR, Ban YH, Kim EJ, Sohng JK, Sim SJ, Yoon YJ. Heterologous production of epothilones B and D in Streptomyces venezuelae. Appl Microbiol Biotechnol. 2008 Nov;81(1):109-17. Epub 2008 Sep 4. PubMed PMID: 18769916.

12: Kuppens IE. Current state of the art of new tubulin inhibitors in the clinic. Curr Clin Pharmacol. 2006 Jan;1(1):57-70. Review. PubMed PMID: 18666378.

13: Donovan D, Vahdat LT. Epothilones: clinical update and future directions. Oncology (Williston Park). 2008 Apr 15;22(4):408-16; discussion 416, 421, 424 passim. Review. PubMed PMID: 18472615.

14: Vahdat LT. Clinical studies with epothilones for the treatment of metastatic breast cancer. Semin Oncol. 2008 Apr;35(2 Suppl 2):S22-30; quiz S40. Review. PubMed PMID: 18410796.

15: Burris HA 3rd. Preclinical investigations with epothilones in breast cancer models. Semin Oncol. 2008 Apr;35(2 Suppl 2):S15-21; quiz S39. Review. PubMed PMID: 18410795.

16: Harrison M, Swanton C. Epothilones and new analogues of the microtubule modulators in taxane-resistant disease. Expert Opin Investig Drugs. 2008 Apr;17(4):523-46. Review. PubMed PMID: 18363517.

17: Lee SH, Son SM, Son DJ, Kim SM, Kim TJ, Song S, Moon DC, Lee HW, Ryu JC, Yoon DY, Hong JT. Epothilones induce human colon cancer SW620 cell apoptosis via the tubulin polymerization independent activation of the nuclear factor-kappaB/IkappaB kinase signal pathway. Mol Cancer Ther. 2007 Oct;6(10):2786-97. PubMed PMID: 17938270.

18: Fumoleau P, Coudert B, Isambert N, Ferrant E. Novel tubulin-targeting agents: anticancer activity and pharmacologic profile of epothilones and related analogues. Ann Oncol. 2007 Jul;18 Suppl 5:v9-15. Review. PubMed PMID: 17656562.

19: Kim TJ, Lim Y, Kim DW, Kwon JS, Son JH, Jin YR, Son DJ, Jung JC, Avery MA, Hong JT, Yun YP. Epothilone D, a microtubule-stabilizing compound, inhibits neointimal hyperplasia after rat carotid artery injury by cell cycle arrest via regulation of G1-checkpoint proteins. Vascul Pharmacol. 2007 Oct;47(4):229-37. Epub 2007 Jul 5. PubMed PMID: 17706465.

20: Beer TM, Higano CS, Saleh M, Dreicer R, Hudes G, Picus J, Rarick M, Fehrenbacher L, Hannah AL. Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel. Invest New Drugs. 2007 Dec;25(6):565-70. Epub 2007 Jul 7. PubMed PMID: 17618407.

21: End N, Furet P, van Campenhout N, Wartmann M, Altmann KH. Total synthesis and biological evaluation of a C(10)/C(12)-phenylene-bridged analog of epothilone D. Chem Biodivers. 2004 Nov;1(11):1771-84. PubMed PMID: 17191815.

22: Verrills NM, Po'uha ST, Liu ML, Liaw TY, Larsen MR, Ivery MT, Marshall GM, Gunning PW, Kavallaris M. Alterations in gamma-actin and tubulin-targeted drug resistance in childhood leukemia. J Natl Cancer Inst. 2006 Oct 4;98(19):1363-74. PubMed PMID: 17018783.

23: Andrieux A, Salin P, Schweitzer A, Bégou M, Pachoud B, Brun P, Gory-Fauré S, Kujala P, Suaud-Chagny MF, Höfle G, Job D. Microtubule stabilizer ameliorates synaptic function and behavior in a mouse model for schizophrenia. Biol Psychiatry. 2006 Dec 1;60(11):1224-30. Epub 2006 Jun 27. PubMed PMID: 16806091.

24: Hearn BR, Zhang D, Li Y, Myles DC. C-15 thiazol-4-yl analogues of (E)-9,10-didehydroepothilone D: synthesis and cytotoxicity. Org Lett. 2006 Jul 6;8(14):3057-9. PubMed PMID: 16805551.

25: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 May;28(4):233-77. PubMed PMID: 16801985.

26: Wang Z, Wang H, Rhie JK, Covey JM, Liang P, Wang S, Wang C, Hu Y, Prasad G, Nan L, Hill DL, Zhang R. Determination of desoxyepothilone B in nude mice plasma by liquid-liquid extraction and reversed-phase high-performance liquid chromatography. J Pharm Biomed Anal. 2006 Sep 18;42(2):272-6. Epub 2006 Apr 17. PubMed PMID: 16616824.

27: Mutka SC, Carney JR, Liu Y, Kennedy J. Heterologous production of epothilone C and D in Escherichia coli. Biochemistry. 2006 Jan 31;45(4):1321-30. PubMed PMID: 16430229.

28: Lee JJ, Swain SM. Development of novel chemotherapeutic agents to evade the mechanisms of multidrug resistance (MDR). Semin Oncol. 2005 Dec;32(6 Suppl 7):S22-6. Review. PubMed PMID: 16360719.

29: Frykman SA, Tsuruta H, Licari PJ. Assessment of fed-batch, semicontinuous, and continuous epothilone D production processes. Biotechnol Prog. 2005 Jul-Aug;21(4):1102-8. PubMed PMID: 16080689.

30: Wu KD, Cho YS, Katz J, Ponomarev V, Chen-Kiang S, Danishefsky SJ, Moore MA. Investigation of antitumor effects of synthetic epothilone analogs in human myeloma models in vitro and in vivo. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10640-5. Epub 2005 Jul 19. PubMed PMID: 16030145; PubMed Central PMCID: PMC1180795.

31: Hause G, Lischewski S, Wessjohann LA, Hause B. Epothilone D affects cell cycle and microtubular pattern in plant cells. J Exp Bot. 2005 Aug;56(418):2131-7. Epub 2005 Jun 20. PubMed PMID: 15967777.

32: Wang H, Wang Z, Wang S, Li M, Nan L, Rhie JK, Covey JM, Zhang R, Hill DL. Preclinical pharmacology of epothilone D, a novel tubulin-stabilizing antitumor agent. Cancer Chemother Pharmacol. 2005 Sep;56(3):255-60. Epub 2005 May 3. PubMed PMID: 15868148.

33: Broadrup RL, Sundar HM, Swindell CS. Total synthesis of 12,13-desoxyepothilone B (Epothilone D). Bioorg Chem. 2005 Apr;33(2):116-33. Epub 2004 Dec 15. PubMed PMID: 15788167.

34: Gaich T, Mulzer J. Synthesis of epothilones via a silicon-tethered RCM reaction. Org Lett. 2005 Mar 31;7(7):1311-3. PubMed PMID: 15787494.

35: Bergstralh DT, Taxman DJ, Chou TC, Danishefsky SJ, Ting JP. A comparison of signaling activities induced by Taxol and desoxyepothilone B. J Chemother. 2004 Dec;16(6):563-76. PubMed PMID: 15700849.

36: Jung JC, Kache R, Vines KK, Zheng YS, Bijoy P, Valluri M, Avery MA. Total syntheses of epothilones B and d. J Org Chem. 2004 Dec 24;69(26):9269-84. PubMed PMID: 15609966.

37: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Sep;26(7):587-612. Review. PubMed PMID: 15538546.

38: Jumaa M, Carlson B, Chimilio L, Silchenko S, Stella VJ. Kinetics and mechanism of degradation of epothilone-D: an experimental anticancer agent. J Pharm Sci. 2004 Dec;93(12):2953-61. PubMed PMID: 15459947.

39: Rivkin A, Yoshimura F, Gabarda AE, Cho YS, Chou TC, Dong H, Danishefsky SJ. Discovery of (E)-9,10-dehydroepothilones through chemical synthesis: on the emergence of 26-trifluoro-(E)-9,10-dehydro-12,13-desoxyepothilone B as a promising anticancer drug candidate. J Am Chem Soc. 2004 Sep 8;126(35):10913-22. PubMed PMID: 15339176.

40: Kolman A. Epothilone D (Kosan/Roche). Curr Opin Investig Drugs. 2004 Jun;5(6):657-67. Review. PubMed PMID: 15242255.

41: Schinzer D, Bourguet E, Ducki S. Synthesis of furano-epothilone D. Chemistry. 2004 Jul 5;10(13):3217-24. PubMed PMID: 15224330.

42: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Apr;26(3):211-44. PubMed PMID: 15148527.

43: Altmann KH, Flörsheimer A, O'Reilly T, Wartmann M. 4. The natural products epothilones A and B as lead structures for anticancer drug discovery: chemistry, biology, and SAR studies. Prog Med Chem. 2004;42:171-205. Review. PubMed PMID: 15003721.

44: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Jan-Feb;26(1):53-84. Review. PubMed PMID: 14988742.

45: Dietzmann A, Kanakis D, Kirches E, Kropf S, Mawrin C, Dietzmann K. Nanomolar concentrations of epothilone D inhibit the proliferation of glioma cells and severely affect their tubulin cytoskeleton. J Neurooncol. 2003 Nov;65(2):99-106. PubMed PMID: 14686728.

46: Nagano S, Li H, Shimizu H, Nishida C, Ogura H, Ortiz de Montellano PR, Poulos TL. Crystal structures of epothilone D-bound, epothilone B-bound, and substrate-free forms of cytochrome P450epoK. J Biol Chem. 2003 Nov 7;278(45):44886-93. Epub 2003 Aug 21. PubMed PMID: 12933799.

47: Verrills NM, Flemming CL, Liu M, Ivery MT, Cobon GS, Norris MD, Haber M, Kavallaris M. Microtubule alterations and mutations induced by desoxyepothilone B: implications for drug-target interactions. Chem Biol. 2003 Jul;10(7):597-607. PubMed PMID: 12890533.

48: Tang L, Qiu RG, Li Y, Katz L. Generation of novel epothilone analogs with cytotoxic activity by biotransformation. J Antibiot (Tokyo). 2003 Jan;56(1):16-23. PubMed PMID: 12670045.

49: Rivkin A, Yoshimura F, Gabarda AE, Chou TC, Dong H, Tong WP, Danishefsky SJ. 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 Mar 12;125(10):2899-901. PubMed PMID: 12617656.

50: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2002 Nov;24(9):615-43. PubMed PMID: 12616707.

51: Kealey JT. Creating polyketide diversity through genetic engineering. Front Biosci. 2003 Jan 1;8:c1-13. Review. PubMed PMID: 12456305.

52: Rivkin A, Njardarson JT, Biswas K, Chou TC, 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. J Org Chem. 2002 Nov 1;67(22):7737-40. PubMed PMID: 12398497.

53: Chappell MD, Harris CR, Kuduk SD, Balog A, Wu Z, Zhang F, Lee CB, Stachel SJ, Danishefsky SJ, Chou TC, Guan Y. 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 Nov 1;67(22):7730-6. PubMed PMID: 12398496.

54: Julien B, Shah S. Heterologous expression of epothilone biosynthetic genes in Myxococcus xanthus. Antimicrob Agents Chemother. 2002 Sep;46(9):2772-8. PubMed PMID: 12183227; PubMed Central PMCID: PMC127399.

55: Biswas K, Lin H, Njardarson JT, Chappell MD, Chou TC, Guan Y, Tong WP, He L, Horwitz SB, Danishefsky SJ. Highly concise routes to epothilones: the total synthesis and evaluation of epothilone 490. J Am Chem Soc. 2002 Aug 21;124(33):9825-32. PubMed PMID: 12175242.

56: Arslanian RL, Tang L, Blough S, Ma W, Qiu RG, Katz L, Carney JR. A new cytotoxic epothilone from modified polyketide synthases heterologously expressed in Myxococcus xanthus. J Nat Prod. 2002 Jul;65(7):1061-4. PubMed PMID: 12141877.

57: Arslanian RL, Parker CD, Wang PK, McIntire JR, Lau J, Starks C, Licari PJ. Large-scale isolation and crystallization of epothilone D from Myxococcus xanthus cultures. J Nat Prod. 2002 Apr;65(4):570-2. PubMed PMID: 11975503.

58: Frykman S, Tsuruta H, Lau J, Regentin R, Ou S, Reeves C, Carney J, Santi D, Licari P. Modulation of epothilone analog production through media design. J Ind Microbiol Biotechnol. 2002 Jan;28(1):17-20. PubMed PMID: 11938466.

59: Lau J, Frykman S, Regentin R, Ou S, Tsuruta H, Licari P. Optimizing the heterologous production of epothilone D in Myxococcus xanthus. Biotechnol Bioeng. 2002 May 5;78(3):280-8. PubMed PMID: 11920444.

60: White JD, Sundermann KF, Wartmann M. Synthesis, conformational analysis, and bioassay of 9,10-didehydroepothilone D. Org Lett. 2002 Mar 21;4(6):995-7. PubMed PMID: 11893205.

61: Hertweck C. The multiplasmid approach: a new perspective for combinatorial biosynthesis. Chembiochem. 2000 Aug 18;1(2):103-6. Review. PubMed PMID: 11828403.

62: Chen H, O'Connor S, Cane DE, Walsh CT. Epothilone biosynthesis: assembly of the methylthiazolylcarboxy starter unit on the EpoB subunit. Chem Biol. 2001 Sep;8(9):899-912. PubMed PMID: 11564558.

63: Lichtner RB, Rotgeri A, Bunte T, Buchmann B, Hoffmann J, Schwede W, Skuballa W, Klar U. Subcellular distribution of epothilones in human tumor cells. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11743-8. Epub 2001 Sep 18. PubMed PMID: 11562452; PubMed Central PMCID: PMC58800.

64: 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 Jul;64(7):847-56. PubMed PMID: 11473410.

65: Lee CB, Wu Z, Zhang F, Chappell MD, Stachel SJ, Chou TC, Guan Y, Danishefsky SJ. Insights into long-range structural effects on the stereochemistry of aldol condensations: a practical total synthesis of desoxyepothilone F. J Am Chem Soc. 2001 Jun 6;123(22):5249-59. PubMed PMID: 11457387.

66: Taylor RE, Chen Y. Total synthesis of epothilones B and D. Org Lett. 2001 Jul 12;3(14):2221-4. PubMed PMID: 11440584.

67: Chou TC, O'Connor OA, Tong WP, Guan Y, Zhang ZG, Stachel SJ, Lee C, Danishefsky SJ. 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 U S A. 2001 Jul 3;98(14):8113-8. PubMed PMID: 11438750; PubMed Central PMCID: PMC35476.

68: Stachel SJ, Lee CB, Spassova M, Chappell MD, Bornmann WG, Danishefsky SJ, Chou TC, Guan Y. On the interactivity of complex synthesis and tumor pharmacology in the drug discovery process: total synthesis and comparative in vivo evaluations of the 15-aza epothilones. J Org Chem. 2001 Jun 15;66(12):4369-78. PubMed PMID: 11397179.

69: 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 Jun 13;123(23):5407-13. Erratum in: J Am Chem Soc. 2003 M ar 12;125(10):3190.. PubMed PMID: 11389619.

70: Sinha SC, Sun J, Miller GP, Wartmann M, Lerner RA. Catalytic antibody route to the naturally occurring epothilones: total synthesis of epothilones A-F. Chemistry. 2001 Apr 17;7(8):1691-702. PubMed PMID: 11349910.

71: Altmann KH, Bold G, Caravatti G, Flörsheimer A, Guagnano V, Wartmann M. Synthesis and biological evaluation of highly potent analogues of epothilones B and D. Bioorg Med Chem Lett. 2000 Dec 18;10(24):2765-8. PubMed PMID: 11133086.

72: Mulzer J, Mantoulidis A, Ohler E. Total syntheses of epothilones B and D. J Org Chem. 2000 Nov 3;65(22):7456-67. PubMed PMID: 11076603.

73: Lee CB, Chou TC, Zhang XG, Wang ZG, Kuduk SD, Chappell MD, Stachel SJ, Danishefsky SJ. 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 Oct 6;65(20):6525-33. PubMed PMID: 11052097.

74: Stachel SJ, Chappell MD, Lee CB, Danishefsky SJ, Chou TC, He L, Horwitz SB. On the total synthesis and preliminary biological evaluations of 15(R) and 15(S) aza-dEpoB: a Mitsunobu inversion at C15 in pre-epothilone fragments. Org Lett. 2000 Jun 1;2(11):1637-9. PubMed PMID: 10841498.

75: 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. 2000 Jun 1;2(11):1633-6. PubMed PMID: 10841497.

76: Julien B, Shah S, Ziermann R, Goldman R, Katz L, Khosla C. Isolation and characterization of the epothilone biosynthetic gene cluster from Sorangium cellulosum. Gene. 2000 May 16;249(1-2):153-60. PubMed PMID: 10831849.

77: Altmann KH, 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 May 17;1470(3):M79-91. Review. PubMed PMID: 10799747.

78: Chou TC, Zhang XG, Harris CR, Kuduk SD, Balog A, Savin KA, Bertino JR, Danishefsky SJ. Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15798-802. PubMed PMID: 9861050; PubMed Central PMCID: PMC28124.

79: Chou TC, Zhang XG, Balog A, Su DS, Meng D, Savin K, Bertino JR, Danishefsky SJ. Desoxyepothilone B: an efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone B. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9642-7. PubMed PMID: 9689134; PubMed Central PMCID: PMC21392.