Epothilones as Natural Compounds for Novel Anticancer Drugs Development
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Date
Authors
Villegas, Cecilia
González-Chavarría, Iván
Burgos, Viviana
Iturra-Beiza, Héctor
Ulrich, Henning
Paz, Cristian
González-Chavarría, Iván
Burgos, Viviana
Iturra-Beiza, Héctor
Ulrich, Henning
Paz, Cristian
Authors
Date
Datos de publicación:
10.3390/ijms24076063
Keywords
Anticancer Agents - Clinical Trials - Cytotoxicity - Epothilone Derivates - Epothilones - Refractory Cancer - Taxanes - Capecitabine - Epothilone A - Epothilone B - Ixabepilone - Paclitaxel - Antineoplastic Agents - Capecitabine - Epothilones - Ixabepilone - Paclitaxel - Tubulin Modulators - Antineoplastic Agent - Capecitabine - Epothilone A - Epothilone B - Epothilone Derivative - Ixabepilone - Paclitaxel - Unclassified Drug - Utidelone - Tubulin Modulator - Antineoplastic Activity - Apoptosis - Cancer Cell Line - Cancer Patient - Clinical Practice - Drug Cytotoxicity - Drug Design - Drug Mechanism - Drug Safety - Drug Synthesis - Hek293 Cell Line - Human - Mcf-7 Cell Line - Mda-mb-435 Cell Line - Mes Sa Dx Cell Line - Mes-sa Cell Line - Microtubule Assembly - Nci-adr-res Cell Line - Nonhuman - Ovcar-8 Cell Line - Phase 2 Clinical Trial (topic) - Phase 3 Clinical Trial (topic) - Preclinical Study - Review - Snb-75 Cell Line - Triple Negative Breast Cancer - Tumor Resistance - Neoplasm - Antineoplastic Agents - Capecitabine - Epothilones - Humans - Neoplasms - Paclitaxel - Tubulin Modulators
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Abstract
Epothilone is a natural 16-membered macrolide cytotoxic compound produced by the metabolism of the cellulose-degrading myxobacterium Sorangium cellulosum. This review summarizes results in the study of epothilones against cancer with preclinical results and clinical studies from 2010 2022. Epothilone have mechanisms of action similar to paclitaxel by inducing tubulin polymerization and apoptosis with low susceptibility to tumor resistance mechanisms. It is active against refractory tumors, being superior to paclitaxel in many respects. Since the discovery of epothilones, several derivatives have been synthesized, and most of them have failed in Phases II and III in clinical trials; however, ixabepilone and utidelone are currently used in clinical practice. There is robust evidence that triple-negative breast cancer (TNBC) treatment improves using ixabepilone plus capecitabine or utidelone in combination with capecitabine. In recent years innovative synthetic strategies resulted in the synthesis of new epothilone derivatives with improved activity against refractory tumors with better activities when compared to ixabepilone or taxol. These compounds together with specific delivery mechanisms could be developed in anti-cancer drugs. © 2023 Elsevier B.V., All rights reserved.
Description
Keywords
Anticancer Agents , Clinical Trials , Cytotoxicity , Epothilone Derivates , Epothilones , Refractory Cancer , Taxanes , Capecitabine , Epothilone A , Epothilone B , Ixabepilone , Paclitaxel , Antineoplastic Agents , Capecitabine , Epothilones , Ixabepilone , Paclitaxel , Tubulin Modulators , Antineoplastic Agent , Capecitabine , Epothilone A , Epothilone B , Epothilone Derivative , Ixabepilone , Paclitaxel , Unclassified Drug , Utidelone , Tubulin Modulator , Antineoplastic Activity , Apoptosis , Cancer Cell Line , Cancer Patient , Clinical Practice , Drug Cytotoxicity , Drug Design , Drug Mechanism , Drug Safety , Drug Synthesis , Hek293 Cell Line , Human , Mcf-7 Cell Line , Mda-mb-435 Cell Line , Mes Sa Dx Cell Line , Mes-sa Cell Line , Microtubule Assembly , Nci-adr-res Cell Line , Nonhuman , Ovcar-8 Cell Line , Phase 2 Clinical Trial (topic) , Phase 3 Clinical Trial (topic) , Preclinical Study , Review , Snb-75 Cell Line , Triple Negative Breast Cancer , Tumor Resistance , Neoplasm , Antineoplastic Agents , Capecitabine , Epothilones , Humans , Neoplasms , Paclitaxel , Tubulin Modulators
Citation
10.3390/ijms24076063