caa a22 4500 445878940 CHVBK 20180317145536.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11030-010-9291-0 doi (NATIONALLICENCE)springer-10.1007/s11030-010-9291-0 Diversity through semisynthesis: the chemistry and biological activity of semisynthetic epothilone derivatives [Elektronische Daten] [Karl-Heinz Altmann, Fabienne Gaugaz, Raphael Schiess] 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. Springer Science+Business Media B.V., 2010 Cancer nationallicence Drug discovery nationallicence Epothilones nationallicence Microtubules nationallicence Natural products nationallicence SAR nationallicence Semisynthesis nationallicence Review nationallicence Altmann Karl-Heinz Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, HCI H405, Wolfgang-Pauli-Str. 10, 8093, Zürich, Switzerland aut Gaugaz Fabienne Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Wolfgang-Pauli-Str. 10, 8093, Zürich, Switzerland aut Schiess Raphael Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Wolfgang-Pauli-Str. 10, 8093, Zürich, Switzerland aut Molecular Diversity Springer Netherlands 15/2(2011-05-01), 383-399 1381-1991 15:2<383 2011 15 11030 https://doi.org/10.1007/s11030-010-9291-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-010-9291-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Altmann Karl-Heinz Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, HCI H405, Wolfgang-Pauli-Str. 10, 8093, Zürich, Switzerland aut NATIONALLICENCE 700 1- Gaugaz Fabienne Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Wolfgang-Pauli-Str. 10, 8093, Zürich, Switzerland aut NATIONALLICENCE 700 1- Schiess Raphael Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Wolfgang-Pauli-Str. 10, 8093, Zürich, Switzerland aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/2(2011-05-01), 383-399 1381-1991 15:2<383 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer