Development of tubulin polymerization inhibitors as anticancer agents.

Introduction: Microtubules are intracellular, filamentous, polymeric structures that extend throughout the cytoplasm, composed of α-tubulin and β-tubulin subunits. They regulate many cellular functions including cell polarity, cell shape, mitosis, intracellular transport, cell signaling, gene expression, cell integrity, and are associated with tumorigenesis. Inhibition of tubulin polymerization within tumor cells represents a crucial focus in the pursuit of developing anticancer treatments.

Areas covered: This review focuses on the natural product and their synthetic congeners as tubulin inhibitors along with their site of interaction on tubulin. This review also covers the developed novel tubulin inhibitors and important patents focusing on the development of tubulin inhibition for cancer treatment reported from 2018 to 2023. The scientific and patent literature has been searched on PubMed, Espacenet, ScienceDirect, and Patent Guru from 2018-2023.

Expert opinion: Tubulin is one of the promising targets explored extensively for drug discovery. Compounds binding in the colchicine site could be given importance because they can elude resistance mediated by the P-glycoprotein efflux pump and no colchicine site binding inhibitor is approved by FDA so far. The research on the development of antibody drug conjugates (ADCs) for tubluin polymerization inhibition could be significant strategy for cancer treatment.