Tubulin degradation: Principles, agents, and applications

The microtubule system plays an important role in the mitosis and growth of eukaryotic cells, and it is considered as an appealing and highly successful molecular target for cancer treatment. In fact, microtubule targeting agents, such as paclitaxel and vinblastine, have been approved by FDA for tumor therapy, which have achieved significant therapeutic effects and sales performance. At present, microtubule targeting agents mainly include microtubule-destabilizing agents, microtubule-stabilizing agents, and a few tubulin degradation agents. Although there are few reports about tubulin degradation agents at present, tubulin degradation agents show great potential in overcoming multidrug resistance and reducing neurotoxicity. In addition, some natural drugs could specifically degrade tubulin in tumor cells, but have no effect in normal cells, thus showing a good biosafety profile. Therefore, tubulin degradation agents might exhibit a better application. Currently, some small molecules have been designed to promote tubulin degradation with potent antiproliferative activities, showing the potential for cancer treatment. In this work, we reviewed the reports on tubulin degradation, and focused on the degradation mechanism and important functional groups of chemically synthesized compounds, hoping to provide help for the degradation design of tubulin.

Automated summary

The microtubule system is a crucial target for cancer treatment and various microtubule targeting agents have been approved for tumor therapy. Tubulin degradation agents show potential in overcoming drug resistance and reducing neurotoxicity, and natural drugs can specifically degrade tubulin in tumor cells with good biosafety. Small molecules have been designed to promote tubulin degradation for cancer treatment, and this study reviews the degradation mechanism and important functional groups of chemically synthesized compounds to aid in the design of tubulin degradation.