The epothilones are naturally occurring antimitotic drugs that share with the taxanes a similar mechanism of action without apparent structural similarity. Although photoaffinity labeling and electron crystallographic studies have identified the taxane-binding site on beta-tubulin, similar data are not available for epothilones. To identify tubulin residues important for epothilone binding, we ...

An efficient monoclonal aldolase antibody that proceeds by an enamine mechanism was generated by reactive immunization. Here, this catalyst has been used in the total synthesis of epothilones A (1) and C (3). The starting materials for the synthesis of these molecules have been obtained by using antibody-catalyzed aldol and retro-aldol reactions. These precursors were then converted to epothilo...

Starting from epothilone A±D (1a±2b) obtained by large scale fermentation of the myxobacterium Sorangium cellulosum the thiazole side-chain was extensively modi®ed by substitution, oxidation and replacement. Metallation afforded the C-19 carbanion 4 which was quenched by various carbon and heteroatom electrophiles to give C-19 substituted epothilones 5. Thiazole N-oxides 9 were obtained by trea...

Ixabepilone (Ixempra) is a member of a new class of cytotoxic agents, the epothilones. Epothilones promote tubulin polymerization in vitro and demonstrate antitumor activity. This article reviews the preclinical and clinical data that have led to the approval of ixabepilone for patients with locally advanced or metastatic breast cancer for whom anthracycline and taxane treatments have failed.

Epothilones are a new class of potential antitumor compounds that were isolated from the myxobacterium Sorangium cellulosum. Epothilones have effects on the cytoskeleton similar to those of the antineoplastic drug Taxol. Both compounds inhibit cell proliferation by stabilizing microtubuli, and they compete for the same binding site. In addition, Taxol displays endotoxin-like properties in that ...

Paclitaxel (Taxol) and the epothilones are antimitotic agents that promote the assembly of mammalian tubulin and stabilization of microtubules. The epothilones competitively inhibit the binding of paclitaxel to mammalian brain tubulin, suggesting that the two types of compounds share a common binding site in tubulin, despite the lack of structural similarities. It is known that paclitaxel does ...

Ovarian cancer is the fifth most lethal malignancy in women. The standard treatment of this disease is chemotherapy which is, however, often inefficient. The failure of chemotherapy is due to the developing multidrug resistance and the presence of cancer stem cells. This article describes research on new drugs, which can overcome these limitations. Some of the substances which are effective in ...