HSET, encoded by KIFC1 in humans and Kifc5a in mice, is a minus-end microtubule motor protein which plays a critical role in the assembly of a functional mitotic spindle. CW069 is an allosteric inhibitor of HSET with IC50 value of 75 μM. CW069 treatment led to a significant increase in multipolar spindle formation in N1E-115 cells (control 30%, 100 mM 98%, 200 mM 86%), but not in normal human dermal fibroblast (NHDF) cells[2]. CW069 treatment dose-dependently suppressed cell viability in both the parental and docetaxel(DTX)-resistant prostate cancer cell lines DU145 and C4-2 cells. The combination of DTX and CW069(100μM) significantly reduced cell viability in the DTX-resistant cell lines while DTX alone had little effect, which demonstrated that CW069 re-sensitized DTX-resistant cell lines to DTX treatment[3].
作用机制
CW069 plays the role of HSET inhibitor by interacting with HSET loop 5 cleft.
搜索
