GSK923295

GSK-923295 is a synthetic small-molecule inhibitor of kinesin-5 (KIF11), a motor protein essential for the formation and maintenance of the bipolar mitotic spindle. It was developed by GlaxoSmithKline for use in research on cell division, spindle mechanics, and cancer biology, and is cited in the literature as a tool compound for studying mitotic processes.

GSK-923295 acts by binding to the motor domain of kinesin-5 (Eg5) and inhibiting its ATPase activity. This disrupts the ability of Eg5 to generate the forces required for centrosome separation, leading to defects in spindle bipolarity. In cells treated with the compound, spindle poles often become unfocused or monopolar, resulting in mitotic arrest during M phase and, in some cases, chromosome missegregation and cell death.

In preclinical research, GSK-923295 has demonstrated potent activity in cancer cell models, with inhibitory effects observed in the low nanomolar to sub-nanomolar range in various assays. It has been used to investigate the role of kinesin-5 in spindle dynamics and to explore the therapeutic potential of Eg5 inhibition as an anti-cancer strategy, helping to elucidate determinants of sensitivity and resistance to mitotic inhibitors.

Clinical development details for GSK-923295 are limited in publicly available sources. The compound is primarily referenced in the context of research on kinesin-5 and mitosis, and, like other Eg5 inhibitors, translational challenges have tempered enthusiasm for pursuing broad clinical approval.