Molecular Diversity

, Volume 15, Issue 2, pp 383–399 | Cite as

Diversity through semisynthesis: the chemistry and biological activity of semisynthetic epothilone derivatives

  • Karl-Heinz Altmann
  • Fabienne Z. Gaugaz
  • Raphael Schiess
Comprehensive Review


Epothilones are myxobacterial natural products that inhibit human cancer cell growth through the stabilization of cellular microtubules (i.e., a “taxol-like” mechanism of action). They have proven to be highly productive lead structures for anticancer drug discovery, with at least seven epothilone-type agents having entered clinical trials in humans over the last several years. SAR studies on epothilones have included a large number of fully synthetic analogs and semisynthetic derivatives. Previous reviews on the chemistry and biology of epothilones have mostly focused on analogs that were obtained by de novo chemical synthesis. In contrast, the current review provides a comprehensive overview on the chemical transformations that have been investigated for the major epothilones A and B as starting materials, and it discusses the biological activity of the resulting products. Many semisynthetic epothilone derivatives have been found to exhibit potent effects on human cancer cell growth and several of these have been advanced to the stage of clinical development. This includes the epothilone B lactam ixabepilone (Ixempra®, which has been approved by the FDA for the treatment of advanced and metastatic breast cancer.


Cancer Drug discovery Epothilones Microtubules Natural products SAR Semisynthesis Review 


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Karl-Heinz Altmann
    • 1
  • Fabienne Z. Gaugaz
    • 2
  • Raphael Schiess
    • 2
  1. 1.Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical SciencesSwiss Federal Institute of Technology (ETH) ZürichZürichSwitzerland
  2. 2.Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical SciencesSwiss Federal Institute of Technology (ETH) ZürichZürichSwitzerland

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