Tubulin (colchicine binding site) (CBS) (CBS)

Tubulin is a heterodimeric protein composed of alpha and beta subunits that serves as the fundamental building block of microtubules, which are essential for maintaining cell structure, facilitating intracellular transport, and forming the mitotic spindle during cell division (UniProt P07437). The colchicine binding site (CBS) is a well-defined hydrophobic pocket located at the interface between the alpha and beta-tubulin subunits within a single heterodimer (PubMed 22101561). Binding of small molecules to this site prevents the tubulin heterodimer from transitioning from a curved to a straight conformation, a step required for its successful incorporation into the growing microtubule polymer (PubMed 24512319). Consequently, CBS inhibitors act as microtubule-destabilizing agents, leading to the disruption of the mitotic spindle, cell cycle arrest in the G2/M phase, and the induction of apoptosis (PubMed 22101561). While colchicine is a long-standing treatment for inflammatory conditions such as gout and Familial Mediterranean Fever (StatPearls), newer CBS-targeting agents are being developed as potent anti-cancer therapies and vascular disrupting agents (VDAs) that selectively target the disorganized blood vessels of solid tumors (PubMed 24512319).

Other names

Colchicine binding siteCBSTubulin-colchicine domainColchicine siteColchicine binding pocket

Inhibition of microtubule polymerization by binding to the alpha/beta-tubulin interface, preventing the curved-to-straight conformational transition required for microtubule assembly.