SNS-314 is an ATP-competitive, potent and selective inhibitor of Aurora kinases A (IC50=9.0nM), B (IC50=31nM), and C (IC50=3.4nM). SNS-314 demonstrated remarkable speci?city and was found to inhibit only 24 of 219 kinases by greater than 65% when screened at 1uM. Histone H3 phosphorylation was potently inhibited by SNS-314 in all 6 cell lines tested with IC50 values ranging from 9 nM in HCT116 cellsto 60 nM in Calu-6 cells.SNS-314 also displayed signi?cant anti-tumor activity in mouse xenograft models of human breast (MDA-MB-231), prostate (PC-3), lung (H1299 and Calu-6), ovarian (A2780) carcinomas and melanoma (A375).SNS-314 represents a new class of highly potent Aurora kinase inhibitors and is being evaluated in a phase-1 dose escalation study designed to assess safety and tolerability in patients with advanced solid malignancies. |
