Taxanes and other microtubule stabilising agents

Abstract

Paclitaxel (Taxol^®) and docetaxel (Taxotere^®) are relatively new drugs used in cancer therapy and have shown great promise in the treatment of a variety of cancers. The taxane therapy, however, encounters two major problems. One problem is the low solubility of both paclitaxel and docetaxel; the second problem is multi-drug resistance. In the patent literature from 1995 - 1997 these two problems have been the main focus of research in the taxane field. Numerous taxoids have been disclosed with improved solubility, mainly by acylation of the C-2′ and C-7 hydroxyls. To reduce the multi-drug resistance susceptibility of the drugs, alterations on the taxane core and the phenylisoserine ring have been made. The patent literature also reports the discovery of new classes of compounds (epothilones, discodermolides, eleutherobins and sarcodictyins) that are structurally dissimilar from taxanes but have microtubule stabilisation activity and are potent inhibitors of cancer cells and paclitaxel-resistant cancer cells.

• discodermolide
• eleutherobin
• epithilones
• multi-drug resistance
• sarcodictyin
• Taxol
• Taxotere
• water solubility