Epothilones Mechanism of Action and Structure-Activity Relationships

2 Epothilones Mechanism of Action and Structure-Activity Relationships 

Epothilones belong to the class of anticancer drugs that target microtubules, along with paclitaxel (Taxol ), docetaxel (Taxotere ) and some others. All these anticancer drugs function by perturbing the dynamic equUibrium of the 

Since the discovery of the epothilones in 1993, an impressive structure-activity relationship (SAR) profile has emerged from the efforts of many synthetic teams [6-8]. This first led to the definition of a common pharmacophore and SAR for the structurally diverse epothilones [9-12], then to the rational design of new structures. 

Initially, data were collected on crystal structure and conformation of epothilone B in solution [13], together with information on the binding site of epothilone A on a/p-tubulin, using electron crystallography and molecular modelling (Fig. 16.2) 

The most important interactions and conformational properties of the tubulin- 

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