centrinone

Centrinone is a synthetic small-molecule inhibitor described as selective for polo-like kinase 4 (PLK4), a key regulator of centriole duplication in animal cells. By targeting PLK4’s kinase activity, centrinone interferes with the initiation of centriole biogenesis, which is normally restricted to a specific phase of the cell cycle.

Mechanistically, centrinone binds to PLK4 and prevents the formation of new centrioles. In human cell lines treated with centrinone, existing centrioles are not supplemented by new ones, leading to progressive centriole depletion over successive cell divisions. As centriole numbers decline, cells can experience mitotic defects, such as abnormal spindle formation, impaired chromosome segregation, and altered mitotic timing. The severity and outcome of these defects can vary by cell type and treatment conditions.

Discovered and characterized in the mid-2010s, centrinone has become a widely used research tool for studying centriole and centrosome biology. Its effects are generally considered reversible: removal of the compound can allow centriole re-duplication and regeneration of centrosomes, enabling studies of centriole biogenesis dynamics and recovery after PLK4 inhibition.

Applications of centrinone focus on basic research into how centrioles are formed, how centrosome number is maintained, and how centrosome abnormalities contribute to disease processes such as cancer. It is used primarily in cell culture experiments to dissect the regulatory pathways governing centriole duplication and to model the consequences of centrosome deficiency.

Limitations include potential off-target effects at higher concentrations, cytotoxicity in some contexts, and variability in responses across cell types. As a research tool, centrinone is not approved for clinical use.