Abstract
Malignancies are a major cause of morbidity and mortality worldwide. Cancer is a cell disease, characterized by a deviation of the control mechanisms of proliferation and differentiation of cells. Among the treatments available, chemotherapy is often the first choice. Epothilones are a new class of anticancer drugs that act by interacting with cellular microtubules interrupting the proliferation of cancer cells. Many synthetic and semi-synthetic analogues of epothilones have been prepared aiming improvement in effectiveness and tolerability, based on QSAR studies. These analogues have been effective for treatment of tumors resistant to first-line treatments. Six new epothilones are being subjected to clinical trials. Ixabepilone (Ixempra®) was approved by FDA in 2007, patupilone is in phase III clinical trial for ovarian and peritoneum cancer. Sagopilone, desoxiepothilone and KOS-1584 are in phase II clinical trials, for the treatment of recurrent glioblastoma and advanced metastatic breast cancer, metastasic breast cancer and metastatic pulmonary cancer, respectively. Desoxiepothilone reached only phase II trials and BMS-310705 reached phase III/IV trials, but were not approved for clinical use due to adverse effects such as neurotoxicity and severe diarrhea, which were dose-limiting. Furthermore, the low t1/2 (40h) in comparison with other class analogues, does not recommend the clinical use of this derivative. Some other synthetized epothilones presented antineoplastic activity in vitro, but are not yet submitted to clinical studies. Neuropathies and diarrhea are adverse effects presented by some substances of this class of anticancer drugs.
Keywords: Anticancer agents, chemotherapy, ixabepilone, patupilone, sagopilone, structure-activity relationship, semi-syntetic analogs.
Anti-Cancer Agents in Medicinal Chemistry
Title:From Bacteria to Antineoplastic: Epothilones A Successful History
Volume: 13 Issue: 7
Author(s): Samuel Kaiser, Joseane John Muller, Pedro Eduardo Froehlich, Simone Cristina Baggio Gnoatto and Ana Maria Bergold
Affiliation:
Keywords: Anticancer agents, chemotherapy, ixabepilone, patupilone, sagopilone, structure-activity relationship, semi-syntetic analogs.
Abstract: Malignancies are a major cause of morbidity and mortality worldwide. Cancer is a cell disease, characterized by a deviation of the control mechanisms of proliferation and differentiation of cells. Among the treatments available, chemotherapy is often the first choice. Epothilones are a new class of anticancer drugs that act by interacting with cellular microtubules interrupting the proliferation of cancer cells. Many synthetic and semi-synthetic analogues of epothilones have been prepared aiming improvement in effectiveness and tolerability, based on QSAR studies. These analogues have been effective for treatment of tumors resistant to first-line treatments. Six new epothilones are being subjected to clinical trials. Ixabepilone (Ixempra®) was approved by FDA in 2007, patupilone is in phase III clinical trial for ovarian and peritoneum cancer. Sagopilone, desoxiepothilone and KOS-1584 are in phase II clinical trials, for the treatment of recurrent glioblastoma and advanced metastatic breast cancer, metastasic breast cancer and metastatic pulmonary cancer, respectively. Desoxiepothilone reached only phase II trials and BMS-310705 reached phase III/IV trials, but were not approved for clinical use due to adverse effects such as neurotoxicity and severe diarrhea, which were dose-limiting. Furthermore, the low t1/2 (40h) in comparison with other class analogues, does not recommend the clinical use of this derivative. Some other synthetized epothilones presented antineoplastic activity in vitro, but are not yet submitted to clinical studies. Neuropathies and diarrhea are adverse effects presented by some substances of this class of anticancer drugs.
Export Options
About this article
Cite this article as:
Kaiser Samuel, Muller John Joseane, Froehlich Eduardo Pedro, Baggio Gnoatto Cristina Simone and Bergold Maria Ana, From Bacteria to Antineoplastic: Epothilones A Successful History, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (7) . https://dx.doi.org/10.2174/18715206113139990133
DOI https://dx.doi.org/10.2174/18715206113139990133 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Cancer Therapy Through Control of Cell Migration
Current Cancer Drug Targets Antineoplastic Activity of an Old Natural Antidiabetic Biguanide on the Human Thyroid Carcinoma Cell Line
Anti-Cancer Agents in Medicinal Chemistry Current Protein-based Anti-angiogenic Therapeutics
Mini-Reviews in Medicinal Chemistry Importance of Influx and Efflux Systems and Xenobiotic Metabolizing Enzymes in Intratumoral Disposition of Anticancer Agents
Current Cancer Drug Targets Epigenetic Regulators Governing Cancer Stem Cells and Epithelial- Mesenchymal Transition in Oral Squamous Cell Carcinoma
Current Stem Cell Research & Therapy HER2-Mediated Anticancer Drug Delivery: Strategies to Prepare Targeting Ligands Highly Specific for the Receptor
Current Medicinal Chemistry The Endothelin Axis as Therapeutic Target in Human Malignancies: Present and Future
Current Pharmaceutical Design Effects of Polymorphisms of the CYP450 Enzyme Genes on Estrogen Status and the Risk for Osteoporosis
Current Pharmacogenomics Imaging Cellular Receptors in Breast Cancers: An Overview
Current Pharmaceutical Biotechnology The Potential Use of Hormone-Based Therapeutics for the Treatment of Alzheimers Disease
Current Alzheimer Research Plant Coumestans: Recent Advances and Future Perspectives in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry The Emerging Role of EMT-related lncRNAs in Therapy Resistance and their Applications as Biomarkers
Current Medicinal Chemistry Irradiation Toxicity and Inflammatory Bowel Diseases (IBD): Review
Reviews on Recent Clinical Trials Chemoradiotherapy of Human Tumors: Novel Approaches from Nanomedicine
Current Pharmaceutical Design Current Perspectives on Novel Drug Delivery Systems and Approaches for Management of Cervical Cancer: A Comprehensive Review
Current Drug Targets The Prolyl-Aminodipeptidases and their Inhibitors as Therapeutic Targets for Fibrogenic Disorders
Mini-Reviews in Medicinal Chemistry Recent Techniques Used in Reproductive Medicine: Outcomes for Gametes Manipulation
Current Women`s Health Reviews Epigenetic Regulation and Therapeutic Approaches in Cancer
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: Epigenetic Regulation and Human Diseases)
Current Pharmaceutical Design Targeting the PI3K/AKT/mTOR Signaling Pathway in Medulloblastoma
Current Molecular Medicine