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
-
Dietary Polyphenols for Treatment of Alzheimer’s Disease– Future Research and Development
Current Pharmaceutical Biotechnology The Functional Role of Long Non-coding RNA UCA1 in Human Multiple Cancers: a Review Study
Current Molecular Medicine Breast Cancer Chemoprevention: Current Perspectives
Current Enzyme Inhibition The Applicability of mTOR Inhibition in Solid Tumors
Current Cancer Drug Targets Cause and Consequences of Genetic and Epigenetic Alterations in Human Cancer
Current Genomics Microglial dependent protective effects of neuroactive steroids
CNS & Neurological Disorders - Drug Targets Infertility, Pregnancy Loss and Adverse Birth Outcomes in Relation to Maternal Secondhand Tobacco Smoke Exposure
Current Women`s Health Reviews Menstrual and Reproductive Outcomes Following Uterine Artery Fibroid Embolisation: A Literature Review
Current Women`s Health Reviews The Critical Roles of HSC70 in Physiological and Pathological Processes
Current Pharmaceutical Design Combined Treatment with JFKD and Gefitinib Overcomes Drug Resistance in Non-Small Cell Lung Cancer
Current Pharmaceutical Biotechnology Kisspeptin Mediated Signaling in Cancer
Current Topics in Medicinal Chemistry Organosulfur Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry Wet-lab Tested MicroRNA Assays for qPCR Studies with SYBR<sup>®</sup> Green and DNA Primers in Pig Tissues
MicroRNA Heterogeneity in the Pathology and Molecular Biology of Breast Cancer
Current Genomics Anti-Inflammatory Activity of Tetracyclines: Applications to Human Disease
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Chemoprevention with Phytonutrients and Microalgae Products in Chronic Inflammation and Colon Cancer
Current Pharmaceutical Design A Review on the Molecular Mechanisms Involved in the Placental Barrier for Drugs
Current Drug Delivery Evidence-Based Management of Infertile Couples with Repeated Implantation Failure Following IVF
Current Women`s Health Reviews Evaluation of Variances in VEGF-A-D and VEGFR-1-3 Expression in the Ishikawa Endometrial Cancer Cell Line Treated with Salinomycin and Anti-Angiogenic/Lymphangiogenic Effect
Current Pharmaceutical Biotechnology mTOR Targeted Cancer Chemoprevention by Flavonoids
Current Medicinal Chemistry