Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition.

Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent compound reported in this study had an IC50 of 0.027 μM in the enzymatic assay for Aur-A inhibition and IC50s between 0.05 μM and 0.5 μM for the inhibition of proliferation of different tumor cell lines.