Microtubule Targeting Agents

B R Hearn, S J Shaw, and D C Myles, Kosan Biosciences, Hayward, CA, USA © 2007 Elsevier Ltd. All Rights Reserved.

7.04.1 Introduction: Microtubule Targeting Agents 81

7.04.1.1 Microtubule Dynamics and the Cell Cycle 81

7.04.2 Inhibitors of Microtubule Assembly 82

7.04.2.1 Inhibitors Targeting the Vinca Alkaloid Binding Domain 82

7.04.2.1.1 Nonpeptide vinca site inhibitors 82

7.04.2.1.2 Peptides and depsipeptides 86

7.04.2.2 Inhibitors Targeting the Colchicine Alkaloid Binding Domain 88

7.04.2.2.1 Colchicine and analogs 88

7.04.2.2.2 Podophyllotoxin and steganacin 89

7.04.2.2.3 Combretastatins 91

7.04.2.2.4 Flavinoids 93

7.04.2.2.5 Other natural products 93

7.04.2.2.6 Synthetic compounds 95

7.04.2.2.7 Conclusion 98

7.04.3 Microtubule Stabilizers and Promotors of Microtubule Assembly 99

7.04.3.1 Paclitaxel and Related Taxanes 99

7.04.3.2 Epothilones 100

7.04.3.3 Discodermolide 101

7.04.3.4 Other Natural Products 102

7.04.3.5 Synthetic Microtubule-Stabilizing Agents 103

7.04.3.6 Conclusion 104 References 104

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