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 mu M in the enzymatic assay for Aur-A inhibition and IC(50)s between 0.05 mu M and 0.5 mu M for the inhibition of proliferation of different tumor cell lines.