title: Epothilones: From discovery to clinical trials.
abstract: Epothilones are natural compounds isolated from a myxobacterium at the beginning of the 1990s, and showed a remarkable anti-neoplastic activity. They act through the same mechanism of action of paclitaxel, by stabilizing microtubules and inducing apoptosis. Although, their chemical structure, simpler than taxanes, makes them more suitable for derivatization. Their interesting pharmacokinetic and bioavailabilty profiles, and the activity against paclitaxel-resistant cell lines make them interesting therapeutic agents. Here a brief historical perspective of epothilones is presented, since their isolation, the identification of their mechanism of action and activity, to the recent clinical trials.
authors.affiliation: Molecular Graphics Laboratory, Dept. of Integrative Structural and Computational Biology, MB-112F The Scripps Research Institute, 10550 North Torrey Pines Road La Jolla, CA 92037-1000, USA. forli@scripps.edu.
authors.forename: Stefano
authors.initials: S
authors.lastname: Forli
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D015195:Drug Design; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects*; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D050257:Tubulin Modulators; D017239:Paclitaxel