Verubulin and its derivatives: Progress and promise in tubulin-targeted cancer therapy

Verubulin (MPC-6827) is a microtubule-destabilizing agent that binds to the colchicine site of tubulin and has been primarily investigated for the treatment of glioblastoma and other malignancies. Its ability to interfere with microtubule dynamics, induce mitotic arrest, and retain efficacy in multidrug-resistant tumour cells has positioned it as a valuable scaffold in the development of next-generation anticancer agents. Over the past decade, extensive efforts have been dedicated to optimizing verubulin and its derivatives through modifications that enhance potency and selectivity. Additional strategies have aimed to improve metabolic stability and brain penetration to expand their therapeutic window and clinical utility. In addition to its therapeutic applications, the small molecular size and high affinity of verubulin for tubulin have also enabled its exploration as a molecular imaging agent in brain-targeted diagnostic research. This review provides a comprehensive overview of the pharmacological profile, clinical development, and structural evolution of verubulin-based compounds, emphasizing their role in advancing tubulin-targeting strategies in oncology. It also offers a future perspective on the potential of verubulin derivatives and the prospects for new candidates to enter clinical evaluation.