Aurora kinase inhibitors

In 1993, the first homologue of the Aurora kinase family was reported to be isolated using a genetic screen to find mutations in yeast that confer an increasein-ploidy phenotype (Ipl1) (1). Shortly thereafter, subsequent reports further characterized the function of Ipl1 to be involved in the process of chromosome segregation (2,3). A Drosophila homologue was discovered in 1995, when it was shown that mutations in a gene named aurora led to mitotic arrest in which condensed chromosomes were attached to circular monopolar mitotic spindles (4). This name was chosen due to the localization of the aurora protein to the poles of the mitotic spindle, similar to the way an aurora borealis is observed at one of the poles of the earth. Furthermore, the name polo was already used to describe a gene of related function (5), and, to keep with a similar theme, aurora was named after the northern lights. In 1997, Sen and colleagues (6) showed that a putative serine/threonine kinase encoding gene that had been previously mapped to chromosome 20q13 (7) was amplified in human breast cancer cell lines, and they named this human homologue breast tumor amplified kinase (BTAK). In that same year, Kimura et al. further characterized this human homologue by reporting its cell cycle-dependent expression and spindle pole localization in HeLa cells (8), and Bischoff and colleagues showed its amplification in human colorectal cancers and its ability to transform rodent fibroblasts (9). These key early reports catapulted the aurora family of kinases to be closely studied as important mitotic kinases, contributors to tumorigenesis, and potential therapeutic targets.