Discovery and development of the epothilones : a novel class of antineoplastic drugs.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe epothilones are a novel class of antineoplastic agents possessing antitubulin activity. The compounds were originally identified as secondary metabolites produced by the soil-dwelling myxobacterium Sorangium cellulosum. Two major compounds, epothilone A and epothilone B, were purified from the S. cellulosum strain So ce90 and their structures were identified as 16-member macrolides. Initial screening with these compounds revealed a very narrow and selective antifungal activity against the zygomycete, Mucor hiemalis. In addition, strong cytotoxic activity against eukaryotic cells, mouse L929 fibroblasts and human T-24 bladder carcinoma cells was observed. Subsequent studies revealed that epothilones induce tubulin polymerization and enhance microtubule stability. Epothilone-induced stabilisation of microtubules was shown to cause arrest at the G2/M transition of the cell cycle and apoptosis. The compounds are active against cancer cells that have developed resistance to taxanes as a result of acquisition of beta-tubulin overexpression or mutations and against multidrug-resistant cells that overexpress P-glycoprotein or multidrug resistance-associated protein. Thus, epothilones represent a new class of antimicrotubule agents with low susceptibility to key tumour resistance mechanisms.More recently, a range of synthetic and semisynthetic epothilone analogues have been produced to further improve the adverse effect profile (or therapeutic window) and to maximize pharmacokinetic and antitumour properties. Various epothilone analogues have demonstrated activity against many tumour types in preclinical studies and several compounds have been and still are being evaluated in clinical trials. This article reviews the identification and early molecular characterization of the epothilones, which has provided insight into the mode of action of these novel antitumour agents in vivo.
CitationDiscovery and development of the epothilones : a novel class of antineoplastic drugs. 2008, 9 (1):1-10notDrugs R D
AffiliationHelmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany. email@example.com
JournalDrugs in R&D
The following license files are associated with this item:
- Preclinical discovery of ixabepilone, a highly active antineoplastic agent.
- Authors: Lee FY, Borzilleri R, Fairchild CR, Kamath A, Smykla R, Kramer R, Vite G
- Issue date: 2008 Dec
- Efficacy and safety of ixabepilone, a novel epothilone analogue.
- Authors: Pivot X, Dufresne A, Villanueva C
- Issue date: 2007 Apr
- The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90.
- Authors: Molnár I, Schupp T, Ono M, Zirkle R, Milnamow M, Nowak-Thompson B, Engel N, Toupet C, Stratmann A, Cyr DD, Gorlach J, Mayo JM, Hu A, Goff S, Schmid J, Ligon JM
- Issue date: 2000 Feb
- Novel tubulin-targeting agents: anticancer activity and pharmacologic profile of epothilones and related analogues.
- Authors: Fumoleau P, Coudert B, Isambert N, Ferrant E
- Issue date: 2007 Jul
- New natural epothilones from Sorangium cellulosum, strains So ce90/B2 and So ce90/D13: isolation, structure elucidation, and SAR studies.
- Authors: Hardt IH, Steinmetz H, Gerth K, Sasse F, Reichenbach H, Höfle G
- Issue date: 2001 Jul