Cancer cells exhibit unlimited proliferation capacity contributed by overexpression of positive regulators and inhibition of gatekeepers and caretakers of the cell cycle.Aurora kinases are serine/threonine kinases which regulate mitotic progression, centrosome maturation, and spindle assembly.Aurora kinases have been found overexpressed in multiple tumors and contribute to tumor progression.Conversely, down regulation of Aurora kinaseexpression leads to activation of the cell-cycle checkpoints, and thus tumor regression.These characteristics make Aurorakinasesappealing targets for the development of anticancer therapies.Here we present two new small molecules with a furanopyrimidine core, IBPR001 and IBPR002,targeting Aurora kinases and inducing DFG conformation change at the ATP site of Aurora A.The two IBPR compounds show high potency in reducing tumorigenesis in a colorectal cancer xenograft model in athymic nude mice.Human hepatoma up-regulated protein (HURP) is a substrate of Aurora kinase A,which plays a crucial role in the stabilization of kinetochore fibers.The two IBPR compounds, as well as MLN8237, a proven Aurora A kinase inhibitor, effectively eliminated HURP phosphorylation.Furthermore,these compounds revealed that HURP is highly dynamic, trafficking between centrosome andkinetochore driven by Aurora A-dependent phosphorylationand protein phosphatase 1/2A-associated dephosphorylation.These compoundsalso suggest a spatial hierarchical preferenceof HURP in the attachment of microtubules extendingfrom the mother to the daughter centrosome.These findingshelp explain the biology of mitosis and may lead to the developmentof new anticancer compounds.