ARRY-520

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Description

ARRY-520 is a potent and selective kinesin spindle protein (KSP) inhibitor with an IC50 of 15 nM for A2780, CP70 and 01-28 cell lines in vitro. ARRY-520 had low nanomolar antiproliferative activity in tumor cell lines. ARRY-520 effectively reduced cell viability in a time-dependent manner in the Type II EOC cell lines A2780, CP70, and 01–28 but had minimal effect on Paclitaxel-resistant Type I EOC cell lines R182, 01–19b, and R1140. In addition, following ARRY-520 treatment, a significant increase in the activity of caspases- 8, 9, and 3 was observed in a time-dependent manner.ARRY-520 is able to induce the activation of caspase-2 in a time-dependent manner similar to that observed with the other caspases-9, -8, and -3. ARRY-520 is able to down-regulate the constitutive MCP-1 secretion. In addition, ARRY-520 induced a decrease in tumor kinetics in a dose-dependent manner.

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