A virtual screening study aimed at identifying small molecules able to bind at the Hec1-MT interaction domain identified one positive hit compound and two analogs of the hit with high cytotoxic, pro-apoptotic and anti-mitotic activities. The most cytotoxic analog (SM15) was shown to produce ...
The virtual screening process led to the identification of two new SMs (SM15 and SM17) with elevated anti-proliferative, pro-apoptotic and anti-mitotic activities. The molecular interaction of SM15 to MTs had been further clarified. Docking studies on SM15 showed that the compound could ...
To test the function of the Hec1 N-terminal globular domain, we microinjected 9G3 into mitotic PtK1 cells. Antibody 9G3 recognized one major band at ∼75 kDa from PtK1 extracts, consistent with the predicted molecular weight of Hec1 (Chen et al., 1997; Figure 1E). Injected 9G3 conc...
Taken together, these findings demonstrate that stimulation of massive chromosome segregation defects can be used as an anti-cancer strategy through the activation of mitotic catastrophe after a multipolar mitosis. Importantly, this study represents a clear proof of concept that targeting KT proteins ...