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
-
An Overview on Keratinocyte Growth Factor: From the Molecular Properties to Clinical Applications
Protein & Peptide Letters BRCA1 as Target for Breast Cancer Prevention and Therapy
Anti-Cancer Agents in Medicinal Chemistry Decorin Biology, Expression, Function and Therapy in the Cornea
Current Molecular Medicine Meet Our Editorial Board Member
Current Drug Targets Estrogen and Female Lower Urinary Tract Dysfunction
Current Women`s Health Reviews Genomic Instability and Carcinogenesis: An Update
Current Genomics A Qualitative and Quantitative Study of the Innervation of the Human Non Pregnant Uterus
Current Protein & Peptide Science HIV-1 Reactivation Induced by Apicidin Involves Histone Modification in Latently Infected Cells
Current HIV Research Studies on the Pathophysiology and Genetic Basis of Migraine
Current Genomics Adjuvant Hormonal Therapy in Women with Early-stage Breast Cancer
Medicinal Chemistry Multiple Biological Activities of Lactic Acid in Cancer: Influences on Tumor Growth,Angiogenesis and Metastasis
Current Pharmaceutical Design Metformin as a Radiation Modifier; Implications to Normal Tissue Protection and Tumor Sensitization
Current Clinical Pharmacology Estrogen Receptors: Molecular Interactions, Virtual Screening and Future Prospects
Current Topics in Medicinal Chemistry EGFR(S) Inhibitors in the Treatment of Gastro-Intestinal Cancers: Whats New?
Current Drug Targets Endoglin-Targeted Cancer Therapy
Current Drug Delivery Telomerase Inhibitors as Anticancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Salinomycin Modulates the Expression of mRNAs and miRNAs Related to Stemness in Endometrial Cancer
Current Pharmaceutical Biotechnology Human Endometrial and Ovarian Cancer Cells: Histone Deacetylase Inhibitors Exhibit Antiproliferative Activity, Potently Induce Cell Cycle Arrest, and Stimulate Apoptosis
Current Medicinal Chemistry Dual Roles of Sulforaphane in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Induction of Senescent-Like Growth Arrest as a New Target in Anticancer Treatment
Current Cancer Drug Targets