Advances in the clinical potential of pyrimidine analogues as tubulin inhibitors in oncology

Tubulin represents a highly promising anticancer target and several inhibitors have been approved for cancer therapy. However, drug resistance and dose-dependent toxicity have limited clinical application. Recently, some novel pyrimidine derivatives have emerged as tubulin inhibitors, such as Lexibulin and Verubulin, which could provide a promising avenue for discovering highly effective anticancer agents. This review covers a comprehensive overview of structure-activity relationships associated with biological activity, as well as clinical development. Furthermore, we highlight the challenges and future prospects in the development of pyrimidine derivatives targeting tubulin.