Author/Authors :
Kevin M. Foote، نويسنده , , Andrew A. Mortlock، نويسنده , , Nicola M. Heron، نويسنده , , Frederic H. Jung، نويسنده , , George B. Hill، نويسنده , , Georges Pasquet، نويسنده , , Madeleine C. Brady، نويسنده , , Stephen Green، نويسنده , , Simon P. Heaton، نويسنده , , Sarah Kearney، نويسنده , , Nicholas J. Keen، نويسنده , , Rajesh Odedra، نويسنده , , Stephen R. Wedge، نويسنده , , Robert W. Wilkinson، نويسنده ,
Abstract :
A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume.
Keywords :
AURORA , kinase , Pyrazole , Quinazoline
