Anticancer drugs from nature--natural products as a unique source of new microtubule-stabilizing agents.

This review article provides an overview on the current state of research in the area of microtubule-stabilizing agents from natural sources, with a primary focus on the biochemistry, biology, and pharmacology associated with these compounds. A variety of natural products have been discovered over the last decade to inhibit human cancer cell proliferation through a taxol-like mechanism. These compounds represent a whole new range of structurally diverse lead structures for anticancer drug discovery.

[1]  P. Northcote,et al.  Peloruside A: a potent cytotoxic macrolide isolated from the new zealand marine sponge Mycale sp. , 2000, The Journal of organic chemistry.

[2]  R. Croteau,et al.  Random sequencing of an induced Taxus cell cDNA library for identification of clones involved in Taxol biosynthesis , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Kinoshita,et al.  A new antimitotic substance, FR182877. III. Structure determination. , 2000, The Journal of antibiotics.

[4]  K. Giuliano,et al.  Tubulin assembly, taxoid site binding, and cellular effects of the microtubule-stabilizing agent dictyostatin. , 2005, Biochemistry.

[5]  D. Myles.  Chapter 13. Emerging microtubule stabilizing agents for cancer chemotherapy , 2002 .

[6]  K. Savin,et al.  Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[7]  G. Piszczek,et al.  Conformation of microtubule-bound paclitaxel determined by fluorescence spectroscopy and REDOR NMR. , 2000, Biochemistry.

[8]  D. Braguer,et al.  Suppression of microtubule dynamics by discodermolide by a novel mechanism is associated with mitotic arrest and inhibition of tumor cell proliferation. , 2003, Molecular cancer therapeutics.

[9]  T. Mayadas,et al.  Use of a photoactivatable taxol analogue to identify unique cellular targets in murine macrophages: identification of murine CD18 as a major taxol-binding protein and a role for Mac-1 in taxol-induced gene expression. , 1999, Journal of immunology.

[10]  C. Khosla,et al.  Isolation and characterization of the epothilone biosynthetic gene cluster from Sorangium cellulosum. , 2000, Gene.

[11]  C. Fairchild,et al.  Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol). , 1998, Cancer research.

[12]  H. Reichenbach,et al.  N-Oxidation of Epothilone A-C and O-Acyl Rearrangement to C-19- and C-21-Substituted Epothilones. , 1999, Angewandte Chemie.

[13]  T. Chou,et al.  Design and total synthesis of a superior family of epothilone analogues, which eliminate xenograft tumors to a nonrelapsable state. , 2003, Angewandte Chemie.

[14]  P. Giannakakou,et al.  Both microtubule-stabilizing and microtubule-destabilizing drugs inhibit hypoxia-inducible factor-1alpha accumulation and activity by disrupting microtubule function. , 2005, Cancer research.

[15]  D. Kingston.  Taxol, a molecule for all seasons , 2001 .

[16]  Yusheng Wu,et al.  Total synthesis and absolute configuration of the novel microtubule-stabilizing agent peloruside A. , 2003, Angewandte Chemie.

[17]  D. Covell,et al.  Antimitotic peptides and depsipeptides. , 2012, Current medicinal chemistry. Anti-cancer agents.

[18]  S. Cisternino,et al.  Nonlinear accumulation in the brain of the new taxoid TXD258 following saturation of P‐glycoprotein at the blood–brain barrier in mice and rats , 2003, British journal of pharmacology.

[19]  G. Parmigiani,et al.  Targeting Vascular and Avascular Compartments of Tumors with C. novyi-NT and Anti-microtubule Agents , 2004, Cancer biology & therapy.

[20]  M Elofsson,et al.  The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. , 2001, Chemistry & biology.

[21]  M. Avery,et al.  The epothilones and related analogues-a review of their syntheses and anti-cancer activities. , 2005, Current pharmaceutical design.

[22]  Lorenzo Caggiano,et al.  Effects of allylic and homoallylic substituents on the ring closing metathesis reaction used to synthesise simplified eleuthesides , 2003 .

[23]  J. Miller,et al.  Peloruside A enhances apoptosis in H-ras-transformed cells and is cytotoxic to proliferating T cells , 2004, Apoptosis.

[24]  Nathan J Hillson,et al.  Excision of the epothilone synthetase B cyclization domain and demonstration of in trans condensation/cyclodehydration activity. , 2005, Biochemistry.

[25]  J M Ligon,et al.  The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90. , 2000, Chemistry & biology.

[26]  P. Crews,et al.  Fijianolides, polyketide heterocycles from a marine sponge , 1988 .

[27]  K. Nicolaou,et al.  Synthesis of epothilones A and B in solid and solution phase , 1997, Nature.

[28]  Ming Xian,et al.  Toward understanding how the lactone moiety of discodermolide affects activity. , 2005, Journal of the American Chemical Society.

[29]  A. Ritzén,et al.  Recent developments in the chemistry, biology and medicine of the epothilones. , 2001, Chemical communications.

[30]  H. Prinz.  Recent advances in the field of tubulin polymerization inhibitors , 2002, Expert review of anticancer therapy.

[31]  Leslie Wilson,et al.  Synergistic Suppression of Microtubule Dynamics by Discodermolide and Paclitaxel in Non-Small Cell Lung Carcinoma Cells , 2004, Cancer Research.

[32]  Arun K. Ghosh,et al.  The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. , 2002, Biochemistry.

[33]  A. Wozniak,et al.  Phase I Clinical Trial of BMS-247550, A Derivative of Epothilone B, Using Accelerated Titration 2B Design , 2005, Clinical Cancer Research.

[34]  E. Nogales,et al.  A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[35]  D. Panda,et al.  Microtubule dynamics in vitro are regulated by the tubulin isotype composition. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Richard E. Taylor,et al.  Total synthesis of (+)-peloruside A. , 2005, Organic letters.

[37]  J. Carney,et al.  A new cytotoxic epothilone from modified polyketide synthases heterologously expressed in Myxococcus xanthus. , 2002, Journal of natural products.

[38]  D. Budman,et al.  Review: Tubulin Function, Action of Antitubulin Drugs, and New Drug Development , 2005, Cancer investigation.

[39]  A. McPhail,et al.  Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. , 1971, Journal of the American Chemical Society.

[40]  J. Seegers,et al.  The cytotoxic effects of estradiol-17 beta, catecholestradiols and methoxyestradiols on dividing MCF-7 and HeLa cells. , 1989, Journal of steroid biochemistry.

[41]  T. Chou,et al.  On the remarkable antitumor properties of fludelone: how we got there. , 2005 .

[42]  H. Reichenbach,et al.  Studies on the biosynthesis of epothilones: the biosynthetic origin of the carbon skeleton. , 2000, The Journal of antibiotics.

[43]  Richard E. Moore,et al.  Laulimalides. New potent cytotoxic macrolides from a marine sponge and a nudibranch predator , 1988 .

[44]  E. Schwartz,et al.  The Microtubule Binding Drug Laulimalide Inhibits Vascular Endothelial Growth Factor-Induced Human Endothelial Cell Migration and Is Synergistic when Combined with Docetaxel (Taxotere) , 2006, Molecular Pharmacology.

[45]  H. Terano,et al.  FR182876, a new microtubule modulator with high water-solubility, from a Streptomyces. , 2004, The Journal of antibiotics.

[46]  Mayumi Kitagawa,et al.  DJ‐927, a novel oral taxane, overcomes P‐glycoprotein‐mediated multidrug resistance in vitro and in vivo , 2003, Cancer science.

[47]  T. Chou,et al.  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. , 2004, Journal of the American Chemical Society.

[48]  G. Borisy,et al.  Microtubule dynamics at the G2/M transition: abrupt breakdown of cytoplasmic microtubules at nuclear envelope breakdown and implications for spindle morphogenesis , 1996, The Journal of cell biology.

[49]  M. Kavallaris,et al.  Antisense oligonucleotides to class III β-tubulin sensitize drug-resistant cells to Taxol , 1999, British Journal of Cancer.

[50]  F. Lee,et al.  Preclinical pharmacokinetics and oral bioavailability of BMS-310705, a novel epothilone B analog , 2005, Cancer Chemotherapy and Pharmacology.

[51]  K. Garber.  Improved Paclitaxel formulation hints at new chemotherapy approach. , 2004, Journal of the National Cancer Institute.

[52]  Amos B. Smith,et al.  A practical improvement, enhancing the large-scale synthesis of (+)-discodermolide: a third-generation approach. , 2003, Organic letters.

[53]  M. Xian,et al.  Total synthesis of (+)-discodermolide: a highly convergent fourth-generation approach. , 2005, Organic letters.

[54]  Kenneth H. Downing,et al.  Structure of the αβ tubulin dimer by electron crystallography , 1998, Nature.

[55]  Xiuguo Zhang,et al.  Therapeutic cure against human tumor xenografts in nude mice by a microtubule stabilization agent, fludelone, via parenteral or oral route. , 2005, Cancer research.

[56]  E. Pasquier,et al.  Antiangiogenic concentrations of paclitaxel induce an increase in microtubule dynamics in endothelial cells but not in cancer cells. , 2005, Cancer research.

[57]  M. Zucchetti,et al.  IDN5109, a taxane with oral bioavailability and potent antitumor activity. , 2000, Cancer research.

[58]  S. Schreiber,et al.  (+)-Discodermolide binds to microtubules in stoichiometric ratio to tubulin dimers, blocks taxol binding and results in mitotic arrest. , 1996, Chemistry & biology.

[59]  I. Barasoain,et al.  Taxanes: microtubule and centrosome targets, and cell cycle dependent mechanisms of action. , 2003, Current cancer drug targets.

[60]  Leslie Wilson,et al.  βIII-Tubulin Induces Paclitaxel Resistance in Association with Reduced Effects on Microtubule Dynamic Instability* , 2005, Journal of Biological Chemistry.

[61]  S. Haggarty,et al.  Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. , 2000, Chemistry & biology.

[62]  Martha Lovato Tse,et al.  Precursor-directed biosynthesis of epothilone in Escherichia coli. , 2004, Journal of the American Chemical Society.

[63]  M. Xian,et al.  Design, synthesis, and evaluation of carbamate-substituted analogues of (+)-discodermolide. , 2005, Organic letters.

[64]  J. Snyder,et al.  The Taxol Pharmacophore and the T-Taxol Bridging Principle , 2005, Cell cycle.

[65]  C. Bocca,et al.  Microtubule-interfering activity of parthenolide. , 2004, Chemico-biological interactions.

[66]  Jeremy P. Scott,et al.  1,6-asymmetric induction in boron-mediated aldol reactions: application to a practical total synthesis of (+)-discodermolide. , 2003, Organic letters.

[67]  L. Garraway,et al.  MDR1 inhibition: less resistance or less relevance? , 2002, European journal of cancer.

[68]  Yaoquan Liu,et al.  Heterologous production of epothilone C and D in Escherichia coli. , 2006, Biochemistry.

[69]  Ó. Delgado,et al.  Total synthesis and configurational assignment of (-)-dictyostatin, a microtubule-stabilizing macrolide of marine sponge origin. , 2004, Angewandte Chemie.

[70]  D. Kingston,et al.  Anticancer Agents from Natural Products , 2005 .

[71]  R. Rosell,et al.  Paclitaxel resistance in non-small-cell lung cancer associated with beta-tubulin gene mutations. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[72]  G. Bernardinelli,et al.  New Cytotoxic Macrolides from the Sponge Fasciospongia rimosa , 1996 .

[73]  H. Rosenkranz,et al.  Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. , 1996, Biochemistry.

[74]  N. Rosen,et al.  Heat shock protein 90 mediates macrophage activation by Taxol and bacterial lipopolysaccharide. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[75]  Nicolas Winssinger,et al.  SOLID AND SOLUTION PHASE SYNTHESIS AND BIOLOGICAL EVALUATION OF COMBINATORIAL SARCODICTYIN LIBRARIES , 1998 .

[76]  K. Giuliano,et al.  Synthesis and biological assessment of simplified analogues of the potent microtubule stabilizer (+)-discodermolide. , 2003, Bioorganic & medicinal chemistry.

[77]  I. Ojima,et al.  Recent strategies in the development of taxane anticancer drugs , 2000 .

[78]  M. Grever,et al.  The taxol supply crisis. New NCI policies for handling the large-scale production of novel natural product anticancer and anti-HIV agents. , 1993, Journal of natural products.

[79]  T. Fojo,et al.  Discodermolide: just another microtubule-stabilizing agent? No! A lesson in synergy. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[80]  S. Chen‐Kiang,et al.  Investigation of antitumor effects of synthetic epothilone analogs in human myeloma models in vitro and in vivo. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[81]  T. Chou,et al.  Highly concise routes to epothilones: the total synthesis and evaluation of epothilone 490. , 2002, Journal of the American Chemical Society.

[82]  F. Guéritte.  General and recent aspects of the chemistry and structure-activity relationships of taxoids. , 2001, Current pharmaceutical design.

[83]  C. Bocca,et al.  A sesquiterpene lactone, costunolide, interacts with microtubule protein and inhibits the growth of MCF-7 cells. , 2004, Chemico-biological interactions.

[84]  S. Shah,et al.  Heterologous Expression of Epothilone Biosynthetic Genes in Myxococcus xanthus , 2002, Antimicrobial Agents and Chemotherapy.

[85]  S. Turner,et al.  In Vivo Measurement of Microtubule Dynamics Using Stable Isotope Labeling with Heavy Water , 2004, Journal of Biological Chemistry.

[86]  Alex Matter,et al.  Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug , 2002, Nature Reviews Drug Discovery.

[87]  M. Botta,et al.  3D QSAR models of interactions between beta-tubulin and microtubule stabilizing antimitotic agents (MSAA): a survey on taxanes and epothilones. , 2004, Current topics in medicinal chemistry.

[88]  M. Hino,et al.  A new antimitotic substance, FR182877. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities. , 2000, The Journal of antibiotics.

[89]  M. LaMarche,et al.  Solution structure of (+)-discodermolide. , 2001, Organic letters.

[90]  M. Kavallaris,et al.  Microtubule alterations and resistance to tubulin-binding agents (review). , 2002, International journal of oncology.

[91]  Arun K. Ghosh,et al.  Laulimalide and paclitaxel: a comparison of their effects on tubulin assembly and their synergistic action when present simultaneously. , 2004, Molecular pharmacology.

[92]  H. Floss,et al.  Biosynthesis of taxoids. Mode of formation of the taxol side chain , 1993 .

[93]  P. Wender,et al.  Microtubule-stabilizing agents based on designed laulimalide analogues. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Gerlach,et al.  Total Synthesis of the Antimicrotubule Agent (+)-Discodermolide Using Boron-Mediated Aldol Reactions of Chiral Ketones. , 2000, Angewandte Chemie.

[95]  F. Lee,et al.  Preclinical antitumor activity of two novel taxanes , 2000, Cancer Chemotherapy and Pharmacology.

[96]  E. Lazarides,et al.  Taxol-Induced Mitotic Block Triggers Rapid Onset of a p53-Independent Apoptotic Pathway , 1995, Molecular medicine.

[97]  P. Giannakakou,et al.  The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (Taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant cells. , 1997, Molecular pharmacology.

[98]  J. Seegers,et al.  Effects of 17β-Estradiol Metabolites on Cell Cycle Events in MCF-7 Cells , 1992 .

[99]  C. Bocca,et al.  Microtubule-interacting activity and cytotoxicity of the prenylated coumarin ferulenol. , 2002, Planta medica.

[100]  L. Chung,et al.  Elucidating the mechanism of cis double bond formation in epothilone biosynthesis. , 2004, Journal of the American Chemical Society.

[101]  I. Barasoain,et al.  Design, synthesis and biological evaluation of novel, simplified analogues of laulimalide: modification of the side chain. , 2005, Bioorganic & medicinal chemistry letters.

[102]  Susan Band Horwitz,et al.  Phase I Clinical and Pharmacokinetic Study of BMS-247550, a Novel Derivative of Epothilone B, in Solid Tumors , 2004, Clinical Cancer Research.

[103]  S. Swain,et al.  Development of novel chemotherapeutic agents to evade the mechanisms of multidrug resistance (MDR). , 2005, Seminars in oncology.

[104]  P. Giannakakou,et al.  Activities of the Microtubule-stabilizing Agents Epothilones A and B with Purified Tubulin and in Cells Resistant to Paclitaxel (Taxol®)* , 1997, The Journal of Biological Chemistry.

[105]  Gloria S. Huang,et al.  Potentiation of Taxol Efficacy by Discodermolide in Ovarian Carcinoma Xenograft-Bearing Mice , 2006, Clinical Cancer Research.

[106]  C. Teng,et al.  Antitumor mechanism of evodiamine, a constituent from Chinese herb Evodiae fructus, in human multiple-drug resistant breast cancer NCI/ADR-RES cells in vitro and in vivo. , 2005, Carcinogenesis.

[107]  T. Poulos,et al.  Crystal Structures of Epothilone D-bound, Epothilone B-bound, and Substrate-free Forms of Cytochrome P450epoK* , 2003, Journal of Biological Chemistry.

[108]  E. Rowinsky.  The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. , 1997, Annual review of medicine.

[109]  M. Hino,et al.  A new antimitotic substance, FR182877. II. The mechanism of action. , 2000, The Journal of antibiotics.

[110]  K. Altmann.  Epothilone B and its analogs - a new family of anticancer agents. , 2003, Mini reviews in medicinal chemistry.

[111]  B. Day,et al.  Fluorous mixture synthesis of (-)-dictyostatin and three stereoisomers. , 2006, Organic letters.

[112]  Jing Wen,et al.  Oxidative Stress-mediated Apoptosis , 2002, The Journal of Biological Chemistry.

[113]  W. B. Derry,et al.  Substoichiometric binding of taxol suppresses microtubule dynamics. , 1995, Biochemistry.

[114]  H. Reichenbach,et al.  Epothilone A and B—Novel 16-Membered Macrolides with Cytotoxic Activity: Isolation, Crystal Structure, and Conformation in Solution† , 1996 .

[115]  M. Kavallaris,et al.  Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. , 1997, The Journal of clinical investigation.

[116]  Y. Kawai,et al.  Molecular basis for lipopolysaccharide mimetic action of Taxol™ and flavolipin , 2003, Journal of endotoxin research.

[117]  K. Giuliano,et al.  Synthesis and high content cell-based profiling of simplified analogues of the microtubule stabilizer (+)-discodermolide. , 2002, Molecular cancer therapeutics.

[118]  S. Danishefsky,et al.  Complex Target-Oriented Synthesis in the Drug Discovery Process: A Case History in the dEpoB Series , 1999 .

[119]  F. Cabral,et al.  A ubiquitous beta-tubulin disrupts microtubule assembly and inhibits cell proliferation. , 2004, Molecular biology of the cell.

[120]  Amos B. Smith,et al.  The relationship between Taxol and (+)-discodermolide: synthetic analogs and modeling studies. , 2001, Chemistry & biology.

[121]  C. Obasaju,et al.  Paclitaxel and docetaxel in prostate cancer. , 2001, Hematology/oncology clinics of North America.

[122]  S. Pomponi,et al.  Tubulin polymerizing activity of dictyostatin-1, a polyketide of marine sponge origin. , 2003, Biochemical pharmacology.

[123]  Y. Kashman,et al.  Sarcodictyin A and Two Novel Diterpenoid Glycosides, Eleuthosides A and B, from the Soft Coral Eleutherobia aurea , 1996 .

[124]  E. Lazarides,et al.  Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. , 1995, Cancer research.

[125]  Hailing Yang,et al.  Expression of class III beta-tubulin reduces microtubule assembly and confers resistance to paclitaxel. , 2003, Cell motility and the cytoskeleton.

[126]  T. Mekhail,et al.  Paclitaxel in cancer therapy , 2002, Expert opinion on pharmacotherapy.

[127]  J. Verweij,et al.  The epothilone dilemma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[128]  Ian Paterson,et al.  Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 5: Linkage of Fragments C1-6 and C7-24 and Finale , 2004 .

[129]  S. Kuduk,et al.  A common pharmacophore for cytotoxic natural products that stabilize microtubules. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[130]  H. Reichenbach,et al.  Studies on the biosynthesis of epothilones: the PKS and Epothilone C/D monooxygenase. , 2001, The Journal of antibiotics.

[131]  Toshimasa Tanaka,et al.  GS-164, a small synthetic compound, stimulates tubulin polymerization by a similar mechanism to that of Taxol , 1997, Cancer Chemotherapy and Pharmacology.

[132]  Lie-Chwen Lin,et al.  Evodiamine inhibits in vitro angiogenesis: Implication for antitumorgenicity. , 2006, Life sciences.

[133]  Z. Wang,et al.  A steroid derivative with paclitaxel-like effects on tubulin polymerization. , 2000, Molecular pharmacology.

[134]  W. B. Derry,et al.  Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. , 1996, Cancer research.

[135]  R. Luduena,et al.  Increased microtubule assembly in bovine brain tubulin lacking the type III isotype of beta-tubulin. , 1990, The Journal of biological chemistry.

[136]  T. Fojo,et al.  Epothilones: a novel class of non-taxane microtubule-stabilizing agents. , 2002, Current pharmaceutical design.

[137]  R. W. Janes,et al.  Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein. , 1999, Journal of molecular biology.

[138]  I. Paterson,et al.  A practical synthesis of (+)-discodermolide and analogues: fragment union by complex aldol reactions. , 2001, Journal of the American Chemical Society.

[139]  Ó. Delgado,et al.  Stereochemical determination of dictyostatin, a novel microtubule-stabilising macrolide from the marine sponge Corallistidae sp. , 2004, Chemical communications.

[140]  J. Ting,et al.  Microtubule stabilizing agents: their molecular signaling consequences and the potential for enhancement by drug combination. , 2006, Cancer treatment reviews.

[141]  T. Fojo,et al.  Expression of beta-tubulin isotypes in human ovarian carcinoma xenografts and in a sub-panel of human cancer cell lines from the NCI-Anticancer Drug Screen: correlation with sensitivity to microtubule active agents. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[142]  Lei Zhang,et al.  Synthesis and biological evaluation of (-)-laulimalide analogues. , 2003, Organic letters.

[143]  M. Ogasawara,et al.  Inhibition by evodiamine of hepatocyte growth factor-induced invasion and migration of tumor cells. , 2004, Biological & pharmaceutical bulletin.

[144]  E. J. Sorensen,et al.  An enantioselective synthesis of FR182877 provides a chemical rationalization of its structure and affords multigram quantities of its direct precursor. , 2003, Journal of the American Chemical Society.

[145]  E. Nogales.  Structural insight into microtubule function. , 2001, Annual review of biophysics and biomolecular structure.

[146]  T. Hemscheidt,et al.  Taccalonolides E and A: Plant-derived steroids with microtubule-stabilizing activity. , 2003, Cancer research.

[147]  T. Fojo,et al.  The role of ABC transporters in clinical practice. , 2003, The oncologist.

[148]  D. Braguer,et al.  Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[149]  K. Altmann,et al.  Structure–Activity Relationships in Side‐Chain‐Modified Epothilone Analogues—How Important is the Position of the Nitrogen Atom? , 2006, ChemMedChem.

[150]  Andrew J. Dannenberg,et al.  Regulation of Cyclooxgenase-2 mRNA Stability by Taxanes , 2003, Journal of Biological Chemistry.

[151]  F. Wang,et al.  A highly epothilone B–resistant A549 cell line with mutations in tubulin that confer drug dependence , 2005, Molecular Cancer Therapeutics.

[152]  Ben Cornett,et al.  The Binding Mode of Epothilone A on α,ß-Tubulin by Electron Crystallography , 2004, Science.

[153]  Yaqing Wang,et al.  Paclitaxel resistance in cells with reduced β-tubulin , 2005 .

[154]  J. Andersen.  Taxane Anticancer Agents: Basic Science and Current Status.Gunda I. Georg , Thomas T. Chen , Iwao Ojima , Dolatrai M. Vyas , 1997 .

[155]  K. Altmann,et al.  Patupilone (epothilone B, EPO906) inhibits growth and metastasis of experimental prostate tumors in vivo , 2005, The Prostate.

[156]  Ian Paterson,et al.  The Development of a Practical Total Synthesis of Discodermolide, a Promising Microtubule-Stabilizing Anticancer Agent , 2003 .

[157]  J. Snyder,et al.  The solid state, solution and tubulin-bound conformations of agents that promote microtubule stabilization. , 2012, Current medicinal chemistry. Anti-cancer agents.

[158]  Y. Tanigawara,et al.  Simvastatin and lovastatin, but not pravastatin, interact with MDR1 , 2002, The Journal of pharmacy and pharmacology.

[159]  C. Walsh,et al.  Polyketide-nonribosomal peptide epothilone antitumor agents: the EpoA, B, C subunits , 2003, Journal of Industrial Microbiology and Biotechnology.

[160]  J. Snyder,et al.  The Conformations of Taxol in Chloroform , 2000 .

[161]  G. K. Paul,et al.  Five new discodermolide analogues from the marine sponge Discodermia species. , 2002, Journal of natural products.

[162]  A. Marcus,et al.  Cyclostreptin (FR182877), an antitumor tubulin-polymerizing agent deficient in enhancing tubulin assembly despite its high affinity for the taxoid site. , 2005, Biochemistry.

[163]  S. Horwitz,et al.  Mechanisms of Taxol-induced cell death are concentration dependent. , 1998, Cancer research.

[164]  S. Akira,et al.  CD11b/CD18 Acts in Concert with CD14 and Toll-Like Receptor (TLR) 4 to Elicit Full Lipopolysaccharide and Taxol-Inducible Gene Expression1 2 3 , 2001, The Journal of Immunology.

[165]  U. Klar,et al.  New synthetic inhibitors of microtubule depolymerization. , 1998, Bioorganic & medicinal chemistry letters.

[166]  M. Kavallaris,et al.  Improving the targeting of tubulin-binding agents: lessons from drug resistance studies. , 2005, Current pharmaceutical design.

[167]  S. Akira,et al.  The role of MyD88 and TLR4 in the LPS‐mimetic activity of Taxol , 2001, European journal of immunology.

[168]  C. Starks,et al.  Large-scale isolation and crystallization of epothilone D from Myxococcus xanthus cultures. , 2002, Journal of natural products.

[169]  J. Snyder,et al.  A unified and quantitative receptor model for the microtubule binding of paclitaxel and epothilone. , 1999, Organic letters.

[170]  R. Govindan,et al.  Novel formulations of taxanes: a review. Old wine in a new bottle? , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[171]  B. Day,et al.  Simplified discodermolide analogues: synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents. , 2003, Journal of medicinal chemistry.

[172]  Ian Paterson,et al.  A second-generation total synthesis of (+)-discodermolide: the development of a practical route using solely substrate-based stereocontrol. , 2005, The Journal of organic chemistry.

[173]  K. Altmann,et al.  The biology and medicinal chemistry of epothilones. , 2012, Current medicinal chemistry. Anti-cancer agents.

[174]  G. Bifulco,et al.  Dactylolide, a New Cytotoxic Macrolide from the Vanuatu SpongeDactylospongia sp. , 2001 .

[175]  C. Mitsiades,et al.  Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo. , 2005, Blood.

[176]  K. Nicolaou,et al.  Molecular Design and Chemical Synthesis of a Highly Potent Epothilone , 2006, ChemMedChem.

[177]  E. Hamel.  Antimitotic natural products and their interactions with tubulin , 1996, Medicinal research reviews.

[178]  S. Mani,et al.  Validation of the pharmacodynamics of BMS-247550, an analogue of epothilone B, during a phase I clinical study. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[179]  (-)-FR182877 is a potent and selective inhibitor of carboxylesterase-1. , 2003, Angewandte Chemie.

[180]  I. Ojima,et al.  Recent advances in the medicinal chemistry of taxoids with novel beta-amino acid side chains. , 1999, Current medicinal chemistry.

[181]  Edward L Schwartz,et al.  Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel (Taxotere): association with impaired repositioning of the microtubule organizing center. , 2002, Molecular cancer therapeutics.

[182]  T. Fojo,et al.  Molecular effects of paclitaxel: Myths and reality (a critical review) , 1999, International journal of cancer.

[183]  I. Paterson,et al.  Conformational studies and solution structure of laulimalide and simplified analogues using NMR spectroscopy and molecular modelling , 2005 .

[184]  I. Ahmad,et al.  Hydrolyzable hydrophobic taxanes: synthesis and anti-cancer activities , 2001, Anti-cancer drugs.

[185]  P. Wender,et al.  Laulimalide and synthetic laulimalide analogues are synergistic with paclitaxel and 2-methoxyestradiol. , 2006, Molecular pharmaceutics.

[186]  I. Barasoain,et al.  Microtubule interactions with chemically diverse stabilizing agents: thermodynamics of binding to the paclitaxel site predicts cytotoxicity. , 2005, Chemistry & biology.

[187]  N. Lewis,et al.  Purification and characterization of taxa-4(5),11(12)-diene synthase from Pacific yew (Taxus brevifolia) that catalyzes the first committed step of taxol biosynthesis. , 1995, Archives of biochemistry and biophysics.

[188]  Robert M. Williams,et al.  Studies on Taxol Biosynthesis. Preparation of Taxa-4(20),11(12)-dien-5α-acetoxy-10β-ol by Deoxygenation of a Taxadiene Tetraacetate Obtained from Japanese Yew , 2002 .

[189]  R. Andersen,et al.  Ceratamines, structurally simple microtubule-stabilizing antimitotic agents with unusual cellular effects. , 2005, Cancer research.

[190]  Yasser A. Elnakady,et al.  Mechanism of Action of Tubulysin, an Antimitotic Peptide from Myxobacteria , 2006, Chembiochem : a European journal of chemical biology.

[191]  K. Nicolaou,et al.  Chemical Biology of Epothilones. , 1998, Angewandte Chemie.

[192]  R. Andersen,et al.  Antimitotic diterpenoids from Erythropodium caribaeorum : isolation artifacts and putative biosynthetic intermediates , 2001 .

[193]  Chi Li,et al.  Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[194]  W. Greco,et al.  Effects of orally active taxanes on P-glycoprotein modulation and colon and breast carcinoma drug resistance. , 2001, Journal of the National Cancer Institute.

[195]  H Irschik,et al.  Epothilons A and B: antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties. , 1996, The Journal of antibiotics.

[196]  D. Kingston,et al.  Modified taxols, 8. Deacylation and reacylation of baccatin III. , 1993, Journal of natural products.

[197]  D. Kingston,et al.  A common pharmacophore for Taxol and the epothilones based on the biological activity of a taxane molecule lacking a C-13 side chain. , 2000, Biochemistry.

[198]  P Wadsworth,et al.  Taxol suppresses dynamics of individual microtubules in living human tumor cells. , 1999, Molecular biology of the cell.

[199]  K. Altmann.  The merger of natural product synthesis and medicinal chemistry: on the chemistry and chemical biology of epothilones. , 2004, Organic & biomolecular chemistry.

[200]  S. Barlow,et al.  Resistance to antimitotic drugs in Chinese hamster ovary cells correlates with changes in the level of polymerized tubulin. , 1991, The Journal of biological chemistry.

[201]  E. T. Haar.  Taxanes and other microtubule stabilising agents , 1998 .

[202]  T. Chou,et al.  Synthesis and conformational analysis of (E)-9,10-dehydroepothilone B: a suggestive link between the chemistry and biology of epothilones. , 2003, Angewandte Chemie.

[203]  R. D'Amato,et al.  2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[204]  Z. Wang,et al.  Synthesis of B-ring homologated estradiol analogues that modulate tubulin polymerization and microtubule stability. , 2000, Journal of medicinal chemistry.

[205]  Susan Band Horwitz,et al.  Total Synthesis of (–)‐Epothilone B: An Extension of the Suzuki Coupling Method and Insights into Structure–Activity Relationships of the Epothilones , 1997 .

[206]  K. Altmann.  Recent developments in the chemical biology of epothilones. , 2005, Current pharmaceutical design.

[207]  C. Walsh,et al.  Epothilone biosynthesis: assembly of the methylthiazolylcarboxy starter unit on the EpoB subunit. , 2001, Chemistry & biology.

[208]  M. Jordan,et al.  Microtubules and actin filaments: dynamic targets for cancer chemotherapy. , 1998, Current opinion in cell biology.

[209]  Cragg Gm,et al.  Taxol: the supply issue. , 1991 .

[210]  P. Wender,et al.  Total synthesis and biological evaluation of 11-desmethyllaulimalide, a highly potent simplified laulimalide analogue. , 2006, Organic letters.

[211]  I. E. Kuppens.  Current state of the art of new tubulin inhibitors in the clinic. , 2006, Current clinical pharmacology.

[212]  M. Wartmann,et al.  EPO906 (epothilone B): a promising novel microtubule stabilizer. , 2003, Seminars in oncology.

[213]  A. Greene,et al.  Highly efficient, practical approach to natural taxol , 1988 .

[214]  K. Savin,et al.  Desoxyepothilone B: an efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone B. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[215]  R. Andersen,et al.  Synthetic transformations of eleutherobin reveal new features of its microtubule-stabilizing pharmacophore. , 2001, Journal of the American Chemical Society.

[216]  J. Snyder,et al.  The bioactive Taxol conformation on beta-tubulin: experimental evidence from highly active constrained analogs. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[217]  Susan Band Horwitz,et al.  Mechanisms of Taxol resistance related to microtubules , 2003, Oncogene.

[218]  S. Horwitz,et al.  MUTATIONS IN BETATUBULIN MAP TO DOMAINS INVOLVED IN REGULATION OF MICROTUBULE STABILITY IN EPOTHILONE-RESISTANT CELL LINES , 2001 .

[219]  Michael Stumm,et al.  STI571 enhances the therapeutic index of epothilone B by a tumor-selective increase of drug uptake. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[220]  Jesús Jiménez-Barbero,et al.  NMR determination of the bioactive conformation of peloruside A bound to microtubules. , 2006, Journal of the American Chemical Society.

[221]  G. N. Sastry,et al.  Design, synthesis and cytotoxic studies on the simplified oxy analog of eleutherobin. , 2004, Bioorganic & medicinal chemistry letters.

[222]  C. Fairchild,et al.  Eleutherobin, a New Cytotoxin that Mimics Paclitaxel (Taxol) by Stabilizing Microtubules , 1997 .

[223]  T. Fojo,et al.  Paclitaxel-resistant Human Ovarian Cancer Cells Have Mutant β-Tubulins That Exhibit Impaired Paclitaxel-driven Polymerization* , 1997, The Journal of Biological Chemistry.

[224]  K. Nicolaou,et al.  Designed Epothilones: Combinatorial Synthesis, Tubulin Assembly Properties, abd Cytotoxic Action against Taxol-Resistant Tumor Cells† , 1997 .

[225]  A. Ritzén,et al.  Chemical synthesis and biological evaluation of novel epothilone B and trans-12,13-cyclopropyl epothilone B analogues , 2002 .

[226]  D. Panda,et al.  Dicoumarol: a unique microtubule stabilizing natural product that is synergistic with Taxol. , 2003, Cancer research.

[227]  M. Botta,et al.  Computational comparison of microtubule-stabilising agents laulimalide and peloruside with taxol and colchicine. , 2004, Bioorganic & medicinal chemistry letters.

[228]  S. Ng,et al.  Modulation of drug resistance by α-tubulin in paclitaxel-resistant human lung cancer cell lines , 2000 .

[229]  M. Xian,et al.  Design, synthesis, and evaluation of analogues of (+)-14-normethyldiscodermolide. , 2005, Organic letters.

[230]  Michael L. Shuler,et al.  Taxol®: science and applications. , 1995 .

[231]  M. Kavallaris,et al.  Microtubule alterations and mutations induced by desoxyepothilone B: implications for drug-target interactions. , 2003, Chemistry & biology.

[232]  G. Campiani,et al.  The Seco-Taxane IDN5390 Is Able to Target Class III β-Tubulin and to Overcome Paclitaxel Resistance , 2005 .

[233]  Xiao-tao Chen,et al.  Structure-activity profiles of eleutherobin analogs and their cross-resistance in Taxol-resistant cell lines , 1999, Cancer Chemotherapy and Pharmacology.

[234]  M. Page,et al.  Aquaculture trials for the production of biologically active metabolites in the New Zealand sponge Mycale hentscheli (Demospongiae: Poecilosclerida) , 2005 .

[235]  M. Xian,et al.  Design, synthesis, and biological evaluation of simplified analogues of (+)-discodermolide. Additional insights on the importance of the diene, the C7 hydroxyl, and the lactone. , 2005, Organic letters.

[236]  R. Borzilleri,et al.  Epothilones: new tubulin polymerization agents in preclinical and clinical development , 2002 .

[237]  D. Myles,et al.  A series of 23,24-dihydrodiscodermolide analogues with simplified lactone regions. , 2006, Bioorganic & medicinal chemistry letters.

[238]  I. Paterson,et al.  Development of a third-generation total synthesis of (+)-discodermolide: an expedient Still-Gennari-type fragment coupling utilizing an advanced beta-ketophosphonate. , 2005, The Journal of organic chemistry.

[239]  M. LaMarche,et al.  Evolution of a Gram-Scale Synthesis of (+)-Discodermolide , 2000 .

[240]  Xian-guo He,et al.  Biosynthesis of Taxoids. Mode of Attachment of the Taxol Side Chain , 1994 .

[241]  Soong-Hoon Kim,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 , 2000 .

[242]  Zhong-liang Chen,et al.  Steroidal bitter principles from tacca plantaginea structures of taccalonolide A and B , 1987 .

[243]  R. Croteau,et al.  Mechanism of taxadiene synthase, a diterpene cyclase that catalyzes the first step of taxol biosynthesis in Pacific yew. , 1996, Biochemistry.

[244]  Susan Band Horwitz,et al.  Structure–Activity Relationship of the Epothilones and the First In Vivo Comparison with Paclitaxel† , 1997 .

[245]  Jens Meiler,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. , 2003, Angewandte Chemie.

[246]  P. Teesdale-Spittle,et al.  Peloruside A Does Not Bind to the Taxoid Site on β-Tubulin and Retains Its Activity in Multidrug-Resistant Cell Lines , 2004, Cancer Research.

[247]  G. Hudes,et al.  Altered beta-tubulin isotype expression in paclitaxel-resistant human prostate carcinoma cells. , 1998, British Journal of Cancer.

[248]  T. Chou,et al.  Second-generation epothilones : discovery of fludelone and its extraordinary antitumor properties , 2005 .

[249]  S. Mooberry,et al.  Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. , 1999, Cancer research.

[250]  T. Chou,et al.  REMOTE EFFECTS IN MACROLIDE FORMATION THROUGH RING-FORMING OLEFIN METATHESIS : AN APPLICATION TO THE SYNTHESIS OF FULLY ACTIVE EPOTHILONE CONGENERS , 1997 .

[251]  R. Croteau,et al.  Cytochrome P450-catalyzed hydroxylation of taxa-4(5),11(12)-diene to taxa-4(20),11(12)-dien-5alpha-ol: the first oxygenation step in taxol biosynthesis. , 1996, Chemistry & biology.

[252]  J. Bergerat,et al.  Signal transduction pathways of taxanes-induced apoptosis. , 2003, Current medicinal chemistry. Anti-cancer agents.

[253]  W. Oh,et al.  A retrospective evaluation of second‐line chemotherapy response in hormone‐refractory prostate carcinoma , 2006, Cancer.

[254]  A. Safa,et al.  Taxol Induces Caspase-10-dependent Apoptosis* , 2004, Journal of Biological Chemistry.

[255]  J. Miller,et al.  Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule- stabilizing activity. , 2002, Cancer research.

[256]  R. Himes,et al.  β-Amyloid-Induced Neurodegeneration and Protection by Structurally Diverse Microtubule-Stabilizing Agents , 2005, Journal of Pharmacology and Experimental Therapeutics.

[257]  Nasser M. Rusan,et al.  Cell Cycle-Dependent Changes in Microtubule Dynamics in Living Cells Expressing Green Fluorescent Protein-α Tubulin , 2001 .

[258]  M. Botta,et al.  3D QSAR studies of the interaction between beta-tubulin and microtubule stabilizing antimitotic agents (MSAA). A combined pharmacophore generation and pseudoreceptor modeling approach applied to taxanes and epothilones. , 2003, Farmaco.

[259]  B. Day,et al.  Discodermolide/Dictyostatin hybrids: synthesis and biological evaluation. , 2002, Organic letters.

[260]  W. Eisenreich,et al.  Studies on the biosynthesis of taxol: the taxane carbon skeleton is not of mevalonoid origin. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[261]  M. D’Incalci,et al.  AACR-NCI-EORTC International conference--molecular targets and cancer therapeutics. , 2001, IDrugs : the investigational drugs journal.

[262]  K. Nicolaou,et al.  The coral-derived natural products eleutherobin and sarcodictyins A and B: effects on the assembly of purified tubulin with and without microtubule-associated proteins and binding at the polymer taxoid site. , 1999, Biochemistry.

[263]  Robert M. Williams,et al.  Taxol biosynthesis: Taxane 13α-hydroxylase is a cytochrome P450-dependent monooxygenase , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[264]  M. Jordan,et al.  Microtubules as a target for anticancer drugs , 2004, Nature Reviews Cancer.

[265]  J. Snyder,et al.  The conformations of discodermolide in DMSO. , 2001, Journal of the American Chemical Society.

[266]  S. Horwitz,et al.  The Microtubule Stabilizing Agent Discodermolide is a Potent Inducer of Accelerated Cell Senescence , 2005, Cell cycle.

[267]  H. Reichenbach,et al.  New natural epothilones from Sorangium cellulosum, strains So ce90/B2 and So ce90/D13: isolation, structure elucidation, and SAR studies. , 2001, Journal of natural products.

[268]  F. Dumont,et al.  Immunosuppression by Discodermolide , 1993, Annals of the New York Academy of Sciences.

[269]  Hui Wang,et al.  Preclinical pharmacology of epothilone D, a novel tubulin-stabilizing antitumor agent , 2005, Cancer Chemotherapy and Pharmacology.

[270]  G. Schulte,et al.  Discodermolide: a new bioactive polyhydroxylated lactone from the marine sponge Discodermia dissoluta , 1990 .

[271]  J. Snyder,et al.  The T-Taxol conformation. , 2006, Journal of medicinal chemistry.

[272]  S. Horwitz,et al.  Novel molecules that interact with microtubules and have functional activity similar to Taxol. , 2001, Drug discovery today.

[273]  R. Luduena,et al.  In vitro analysis of microtubule assembly of isotypically pure tubulin dimers. Intrinsic differences in the assembly properties of alpha beta II, alpha beta III, and alpha beta IV tubulin dimers in the absence of microtubule-associated proteins. , 1994, The Journal of biological chemistry.

[274]  A. Bond,et al.  Synthesis of a simplified analogue of eleutherobin via a Claisen rearrangement and ring closing metathesis strategy. , 2005, Chemical communications.

[275]  R. Andersen,et al.  Antimitotic diterpenes from Erythropodium caribaeorum test pharmacophore models for microtubule stabilization. , 2000, Organic letters.

[276]  C. Khosla,et al.  Cloning and heterologous expression of the epothilone gene cluster. , 2000, Science.

[277]  G. Bernardinelli,et al.  Structures and absolute configurations of the marine toxins, latrunculin A and laulimalide , 1996 .

[278]  H. Tabata.  Production of paclitaxel and the related taxanes by cell suspension cultures of Taxus species. , 2006, Current drug targets.

[279]  R. Croteau,et al.  Taxol biosynthesis: Molecular cloning and characterization of a cytochrome P450 taxoid 7 beta-hydroxylase. , 2004, Chemistry & biology.

[280]  F. Pietra,et al.  Sarcodictyin A and Sarcodictyin B, Novel Diterpenoidic Alcohols Esterified by (E)-N(1)-Methylurocanic Acid. Isolation from the Mediterranean Stolonifer Sarcodictyon roseum , 1987 .

[281]  D. Ettinger,et al.  Evaluation of epothilone B analog in advanced soft tissue sarcoma: a phase II study of the phase II consortium. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[282]  Robert M. Long,et al.  Preliminary assessment of the C13-side chain 2'-hydroxylase involved in taxol biosynthesis. , 2005, Biochemical and biophysical research communications.

[283]  S. Hashino,et al.  MyD88 is involved in the signalling pathway for Taxol‐induced apoptosis and TNF‐α expression in human myelomonocytic cells , 2002, British journal of haematology.

[284]  F. Loganzo,et al.  MAC-321, a novel taxane with greater efficacy than paclitaxel and docetaxel in vitro and in vivo. , 2003, Molecular cancer therapeutics.

[285]  M. Lind,et al.  Do β-tubulin mutations have a role in resistance to chemotherapy? , 2004 .

[286]  J. Sludden,et al.  A Phase I and Pharmacokinetic Study of Paclitaxel Poliglumex (XYOTAX), Investigating Both 3-Weekly and 2-Weekly Schedules , 2005, Clinical Cancer Research.

[287]  M. Page,et al.  Spatial and Temporal Variability of Cytotoxic Metabolites in Populations of the New Zealand Sponge Mycale hentscheli , 2005, Journal of Chemical Ecology.

[288]  K. Kinzler,et al.  Discodermolide analogues as the chemical component of combination bacteriolytic therapy. , 2005, Bioorganic & medicinal chemistry letters.

[289]  S. Danishefsky,et al.  Taxol and discodermolide represent a synergistic drug combination in human carcinoma cell lines. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[290]  T. Fojo,et al.  A Phase I clinical trial of ixabepilone (BMS‐247550), an epothilone B analog, administered intravenously on a daily schedule for 3 days , 2005, Cancer.

[291]  C. Fairchild,et al.  Synthesis and biological activity of novel epothilone aziridines. , 2001, Organic letters.

[292]  S. Gunasekera,et al.  Synthetic analogues of the microtubule-stabilizing agent (+)-discodermolide: preparation and biological activity. , 2001, Journal of natural products.

[293]  H. Choy,et al.  Phase II trial of weekly paclitaxel and concurrent radiation therapy for locally advanced non-small cell lung cancer. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[294]  R. Geney,et al.  Recent advances in the new generation taxane anticancer agents. , 2005, Medicinal chemistry (Shariqah (United Arab Emirates)).

[295]  M. Gottesman,et al.  Multidrug resistance in cancer: role of ATP–dependent transporters , 2002, Nature Reviews Cancer.

[296]  Samuel I. Miller,et al.  Human Toll-like receptor 4 recognizes host-specific LPS modifications , 2002, Nature Immunology.

[297]  P. Schiff,et al.  Promotion of microtubule assembly in vitro by taxol , 1979, Nature.

[298]  K. Altmann.  Microtubule-stabilizing agents: a growing class of important anticancer drugs. , 2001, Current opinion in chemical biology.

[299]  C. Fairchild,et al.  Synthesis and antitumor activity of novel C-7 paclitaxel ethers: discovery of BMS-184476. , 2001, Journal of medicinal chemistry.

[300]  M. Jordan,et al.  Suppression of microtubule dynamics by epothilone B is associated with mitotic arrest. , 2003, Cancer research.

[301]  C. Bocca,et al.  Biological properties of jatrophane polyesters, new microtubule-interacting agents , 2002, Cancer Chemotherapy and Pharmacology.

[302]  R. Luduena,et al.  Removal of beta III isotype enhances taxol induced microtubule assembly. , 1993, Cell structure and function.

[303]  N. Lewis,et al.  Cyclization of Geranylgeranyl Diphosphate to Taxa-4 (5), 11 (12) -diene Is the Committed Step of Taxol Biosynthesis in Pacific Yew (*) , 1995, The Journal of Biological Chemistry.

[304]  K. Nicolaou,et al.  Total synthesis of epothilone E and related side-chain modified analogues via a Stille coupling based strategy. , 1999, Bioorganic & medicinal chemistry.

[305]  M. Jordan,et al.  Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[306]  L. Amos,et al.  Microtubule structure and its stabilisation. , 2004, Organic & biomolecular chemistry.

[307]  M. Zucchetti,et al.  Oral efficacy and bioavailability of a novel taxane. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[308]  Fenghua Liu,et al.  Design, total synthesis, and evaluation of C13-C14 cyclopropane analogues of (+)-discodermolide. , 2005, Organic letters.

[309]  James G. Tarrant,et al.  The discovery of BMS-275183: an orally efficacious novel taxane. , 2003, Bioorganic & medicinal chemistry.

[310]  J. Roth,et al.  Potent antitumor activity of 2-methoxyestradiol in human pancreatic cancer cell lines. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[311]  E. Nogales,et al.  Refined structure of alpha beta-tubulin at 3.5 A resolution. , 2001, Journal of molecular biology.

[312]  Robert M. Long,et al.  Taxol biosynthesis: differential transformations of taxadien-5 alpha-ol and its acetate ester by cytochrome P450 hydroxylases from Taxus suspension cells. , 2001, Archives of biochemistry and biophysics.

[313]  M. Ogasawara,et al.  Inhibitory effects of evodiamine on in vitro invasion and experimental lung metastasis of murine colon cancer cells. , 2001, Biological & pharmaceutical bulletin.

[314]  A. Guerriero,et al.  Isolation from the Mediterranean Stolonifern Coral Sarcodictyon roseum of Sarcodictyin C, D, E, and F, novel diterpenodic alcohols esterified by (E)‐ or (Z)‐N(1)‐methylurocanic acid. Failure of the carbon‐skeleton type as a classification criterion , 1988 .

[315]  P. Finn,et al.  The cell cycle, chromatin and cancer: mechanism-based therapeutics come of age. , 2003, Drug discovery today.

[316]  A. Dicker,et al.  Comparison of antiangiogenic activities using paclitaxel (taxol) and docetaxel (taxotere) , 2003, International journal of cancer.

[317]  M. Gottesman.  Mechanisms of cancer drug resistance. , 2002, Annual review of medicine.

[318]  M. Hussain,et al.  Epothilones and the next generation of phase III trials for prostate cancer , 2005, BJU international.

[319]  T. Shuin,et al.  Docetaxel enhances the therapeutic effect of the angiogenesis inhibitor TNP-470 (AGM-1470) in metastatic human transitional cell carcinoma. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[320]  Fenghua Liu,et al.  Design, synthesis and cytotoxicity of 7-deoxy aryl discodermolide analogues. , 2004, Bioorganic & medicinal chemistry letters.

[321]  P. Chacón,et al.  Changes in Microtubule Protofilament Number Induced by Taxol Binding to an Easily Accessible Site , 1998, The Journal of Biological Chemistry.

[322]  D. Zaharevitz,et al.  Chemical synthesis and biological properties of pyridine epothilones. , 2000, Chemistry & biology.

[323]  P. Ortiz de Montellano,et al.  EpoK, a cytochrome P450 involved in biosynthesis of the anticancer agents epothilones A and B. Substrate-mediated rescue of a P450 enzyme. , 2004, Biochemistry.

[324]  J. Snyder,et al.  The binding conformation of Taxol in β-tubulin: A model based on electron crystallographic density , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[325]  H. Kaehlig,et al.  Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues: the power of Sharpless' asymmetric epoxidation. , 2003, The Journal of organic chemistry.

[326]  J. Mulzer,et al.  Microtubule-stabilizing marine metabolite laulimalide and its derivatives: synthetic approaches and antitumor activity. , 2003, Chemical reviews.

[327]  Soong-Hoon Kim,et al.  SAR and pH stability of cyano-substituted epothilones. , 2002, Organic letters.

[328]  S. Ducki,et al.  Synthesis of novel simplified sarcodictyin/eleutherobin analogs with potent microtubule-stabilizing activity, using ring closing metathesis as the key-step , 2003 .

[329]  Alexey Rivkin,et al.  Complex target-oriented total synthesis in the drug discovery process: the discovery of a highly promising family of second generation epothilones. , 2003, Journal of the American Chemical Society.

[330]  R. Longley,et al.  DISCODERMOLIDE—A NEW, MARINE‐DERIVED IMMUNOSUPPRESSIVE COMPOUND: I. IN VITRO STUDIES , 1991, Transplantation.

[331]  David J Newman,et al.  A tale of two tumor targets: topoisomerase I and tubulin. The Wall and Wani contribution to cancer chemotherapy. , 2004, Journal of natural products.

[332]  F. Lee,et al.  BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[333]  X. Yao,et al.  Diterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of Xenopus. , 2002, Journal of natural products.

[334]  C. Simmerling,et al.  Use of the tubulin bound paclitaxel conformation for structure-based rational drug design. , 2005, Chemistry & biology.

[335]  G. Strobel.  Endophytes as sources of bioactive products. , 2003, Microbes and infection.

[336]  M. Boyd,et al.  Isolation and structure of the cancer cell growth inhibitor dictyostatin 1 , 1994 .

[337]  I. Ojima,et al.  Antibody–cytotoxic agent conjugates for cancer therapy , 2005, Expert opinion on drug delivery.

[338]  H. Thaler,et al.  Chemotherapy Induces the Expression of Cyclooxygenase-2 in Non–Small Cell Lung Cancer , 2005, Clinical Cancer Research.