Mitotic kinesins are exclusively involved in the formation and function of the mitotic spindle, and some kinesins are only expressed in proliferating cells. Mitotic kinesin Eg5, encoded by KIF11, is essential for cell division. Dimethylenastron is specific and reversible mitotic motor kinesin Eg5 inhibitor with IC50 value of 200 nM. Growth of HUVECs and lymphatic endothelial cells (LECs) was inhibited by dimethylenastron (DMN) in a dose- and time-dependent manner (0.1-1μM, 24-96 h). U87 gliomas grown on the chicken chorio-allantoic membrane showed reduced numbers of angiogenic capillaries after treatment with a single dose of 10 ug DMN per day[3]. Treatment of PANC1 pancreatic cancer cells with dimethylenastron (3 and 10 μM) for 24 h suppressed the migratory ability of the cancer cells in a concentration-dependent manner, but had no detectable effect on their proliferation[4].
作用机制
Dimethylenastron allosterically inhibits the motor domain ATPase of Eg5 by decreasing the rate of ADP release.
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