Epothilones as Natural Compounds for Novel Anticancer Drugs Development

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.

Automated summary

This review summarizes the preclinical and clinical studies on the anticancer effects of epothilones from 2010 to 2022. Epothilones exhibit similar mechanisms of action to paclitaxel, inducing tubulin polymerization and apoptosis, and have low susceptibility to tumor resistance mechanisms. They are more effective than paclitaxel in combating refractory tumors. While most synthesized epothilone derivatives have failed in clinical trials, ixabepilone and utidelone are currently used in clinical practice. There is robust evidence that ixabepilone plus capecitabine or utidelone in combination with capecitabine improves the treatment of triple-negative breast cancer (TNBC). In recent years, innovative synthetic strategies have led to the development of new epothilone derivatives with improved activity against refractory tumors, surpassing ixabepilone and taxol. These compounds, together with specific delivery mechanisms, hold promise for the development of anticancer drugs.