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.

Mostofthedrugsavailabletodayforthetreatmentofcancerarebasedontheinhibitionofcellproliferationandinductionofcelldeathbyapoptosis.Atthemolecularlevel,themajorityofcytotoxicagentsinterferewithDNAfunction.However,aprominent subclass of compounds, including paclitaxel(taxol), exert their cytotoxic activity by perturbing micro-tubuledynamics.In1993,Hfle,Reichenbach,andcoworkersreportedtheisolationandcharacterizationofanovelclassofcytotoxic polyketide macrolides from the myxobacteriumSorangiumcellulosum,whichwerenamedepothilones(1).