Did you mean: epothilone
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Neuropathology and Applied Neurobiology Oct 2018
Topics: Animals; Mice; Amyotrophic Lateral Sclerosis; Disease Progression; Epothilones; Disease Models, Animal
PubMed: 29437244
DOI: 10.1111/nan.12478 -
Methods in Molecular Medicine 2007Microtubules are found in all eukaryotes and are built from alphabeta-tubulin heterodimers. The alpha-tubulins and beta-tubulins are among the most highly conserved... (Review)
Review
Microtubules are found in all eukaryotes and are built from alphabeta-tubulin heterodimers. The alpha-tubulins and beta-tubulins are among the most highly conserved eukaryotic proteins. Other members of the tubulin family have come to light recently and, like gamma-tubulin, appear to play roles in microtubule nucleation and assembly. Microtubule assembly is accompanied by hydrolysis of GTP associated with beta-tubulin so that microtubules consist principally of "GDP-tubulin" stabilized by a short "GTP cap." Microtubules are polar, cylindrical structures some 25 nm in diameter. Protofilaments made from tubulin heterodimers run lengthwise along the microtubule wall with the beta-tubulin subunit at the microtubule plus end. The crystallographic structures of tubulins are essential to understand in detail microtubule architecture and interactions with stabilizing and destabilizing drugs and proteins.
Topics: Animals; Docetaxel; Epothilones; Eukaryotic Cells; Guanosine Triphosphate; Humans; Hydrolysis; Microtubules; Models, Molecular; Paclitaxel; Protein Structure, Tertiary; Structure-Activity Relationship; Taxoids; Tubulin
PubMed: 18085218
DOI: 10.2119/molecular%20medicine-2006-00038 -
Journal of Clinical Oncology : Official... Dec 2005
Topics: Clinical Trials as Topic; Epothilones; Humans; Neoplasms
PubMed: 16301592
DOI: 10.1200/JCO.2005.03.8844 -
Expert Opinion on Investigational Drugs 2016Endometrial cancer (EC) is the most common gynaecological cancer. Despite significant progress in the multimodality treatment approach, the prognosis remains poor for... (Review)
Review
INTRODUCTION
Endometrial cancer (EC) is the most common gynaecological cancer. Despite significant progress in the multimodality treatment approach, the prognosis remains poor for patients with advanced disease. Thus, there is the necessity of more effective strategies. The microtubule-stabilizing agent ixabepilone is the first drug in this new class of agents that has been approved for metastatic breast cancer treatment. Based on empiric data and on the clinical efficacy demonstrated in breast cancer, several clinical trials were proposed to define its role in EC. The aim of this review is to determine whether ixabepilone improved the clinical outcome in patients with locally advanced, recurrent or metastatic EC.
AREAS COVERED
Preclinical and clinical studies of ixabepilone in endometrial cancer were analyzed and discussed. Data were obtained by searching for English peer-reviewed articles on PubMed, phase I and II studies registered on clincaltrials.gov, and related abstracts recently presented at major international congresses.
EXPERT OPINION
Advanced or recurrent EC still represents a challenge and an unmet need in the panorama of gynaecological malignancies. Ixabepilone's future therapeutic role in EC remains ill defined. Nevertheless, despite its limited efficacy in EC, clinicians treating gynaecological tumours should be aware of its main aspects.
Topics: Animals; Antineoplastic Agents; Endometrial Neoplasms; Epothilones; Female; Humans
PubMed: 26949829
DOI: 10.1517/13543784.2016.1161755 -
European Journal of Medicinal Chemistry Sep 2018Epothilones are a class of 16-membered macrolide compounds targeting microtubules. They have good anticancer activity and their mechanism of action is similar to that of... (Review)
Review
Epothilones are a class of 16-membered macrolide compounds targeting microtubules. They have good anticancer activity and their mechanism of action is similar to that of paclitaxel. Epothilones are also highly active against cancer cells that are resistant to paclitaxel and other anticancer drugs. They have good water solubility, simple structure, and are relatively easy to totally synthesize and or semi-synthesize. These results immediately attracted great interest and research enthusiasm from pharmaceutical companies and academia. Herein, the various synthetic methods of epothilone B and its anticancer activity were summarized and analyzed.
Topics: Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Epothilones; Humans; Molecular Structure; Neoplasms; Structure-Activity Relationship
PubMed: 30149324
DOI: 10.1016/j.ejmech.2018.08.055 -
Current Topics in Medicinal Chemistry 2014Epothilones are natural compounds isolated from a myxobacterium at the beginning of the 1990s, and showed a remarkable anti-neoplastic activity. They act through the... (Review)
Review
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.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Clinical Trials as Topic; Drug Design; Epothilones; Humans; Microtubules; Mitosis; Molecular Docking Simulation; Neoplasms; Paclitaxel; Protein Binding; Structure-Activity Relationship; Tubulin Modulators
PubMed: 25434353
DOI: 10.2174/1568026614666141130095855 -
Expert Opinion on Investigational Drugs Jan 2011Since the introduction of taxane-based chemotherapy for advanced solid tumors in the 1990s, the median overall survival of patients with metastatic breast cancer... (Review)
Review
IMPORTANCE OF THE FIELD
Since the introduction of taxane-based chemotherapy for advanced solid tumors in the 1990s, the median overall survival of patients with metastatic breast cancer increased from 2 years to almost 5 years. Similarly, the 5-year overall survival for ovarian cancer has increased from 30% to more than 40%.
AREAS COVERED IN THIS REVIEW
Patupilone is a novel cytotoxic compound, with similar microtubule-binding and apoptotic properties of taxanes and is active in taxane-resistant cell lines. Over 1200 patients have been treated with patupilone in Phase I - III clinical trials and a wealth of knowledge has accumulated about this compound. This review discusses current pharmacology and data from clinical trials with patupilone from the last seven years.
WHAT THE READER WILL GAIN
We present a comprehensive summary of data from Phase II and III trials, as well as an overview of currently accruing trials.
TAKE HOME MESSAGE
Although patupilone has not demonstrated superiority over pegylated liposomal doxorubicin in a large Phase III trial in relapsed or refractory ovarian cancer, its evaluation is continuing in a range of other malignancies, especially in primary or secondary tumors of the CNS.
Topics: Animals; Antineoplastic Agents; Apoptosis; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Epothilones; Humans; Neoplasms; Survival Rate; Tubulin Modulators
PubMed: 21142807
DOI: 10.1517/13543784.2011.542148 -
Current Drug Targets 2018Epothilones are a class of macrolide compounds. Their activities of tubulin polymerization and microtubule depolymerization inhibition like paclitaxel make them a new... (Comparative Study)
Comparative Study Review
Epothilones are a class of macrolide compounds. Their activities of tubulin polymerization and microtubule depolymerization inhibition like paclitaxel make them a new generation of antimitotic drugs. The mechanism of action is similar to that of paclitaxel, which can bind to tubulin and cause cancer cells to fail to undergo mitosis, thereby causing apoptosis in cancer cells. Epothilone is superior to paclitaxel in anti-tumor spectrum, anti-tumor activity, safety, water solubility and synthetic methods. It is expected to develop into a more effective anti-tumor drug than paclitaxel. Herein, the synthesis methods and activity of epothilone D were summarized and analyzed.
Topics: Cell Survival; Clinical Trials as Topic; Drug Screening Assays, Antitumor; Epothilones; Humans; Mitosis; Neoplasms; Paclitaxel; Tubulin Modulators
PubMed: 30073925
DOI: 10.2174/1389450119666180803122118 -
European Journal of Medicinal Chemistry Apr 2015Modulators of microtubule dynamics have received increasing attention because of their potential to stop cancer growth. Although it belongs to the category of complex... (Review)
Review
Modulators of microtubule dynamics have received increasing attention because of their potential to stop cancer growth. Although it belongs to the category of complex protein-protein interactions (PPIs), which are generally considered difficult to modulate through small molecules, the use of microtubule is considered a well-validated target. There are a number of bioactive natural products and related compounds that are currently in use as drugs or in clinical trials as next generation anti-cancer agents. The present review article is focused on two such bioactive natural products, epothilone and halichondrin B, and covers some of the key papers published after 2005 that outline various synthetic approaches to obtain next generation structural analogs as well as the synthesis of hybrid compounds.
Topics: Animals; Biological Products; Epothilones; Ethers, Cyclic; Humans; Macrolides; Molecular Structure; Structure-Activity Relationship; Tubulin; Tubulin Modulators
PubMed: 25455639
DOI: 10.1016/j.ejmech.2014.10.062 -
Chemical Biology & Drug Design Aug 2020Epothilone is a kind of macrolide compound, which has anticancer activity and strong inhibitory effect on breast cancer and rectal cancer cells. Herein, the chemical and... (Review)
Review
Epothilone is a kind of macrolide compound, which has anticancer activity and strong inhibitory effect on breast cancer and rectal cancer cells. Herein, the chemical and biological synthesis of epothilones and how to improve fermentation yield and separation methods were summarized and discussed.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Ceramics; Drug Screening Assays, Antitumor; Epothilones; Fermentation; Glycosylation; Humans; Mutation; Porosity; Secondary Metabolism; Streptomyces; Structure-Activity Relationship; Surface Properties
PubMed: 32220102
DOI: 10.1111/cbdd.13687