Aurora kinase family (AURK)

The Aurora kinase family comprises three highly conserved serine/threonine kinases—Aurora A, Aurora B, and Aurora C—that are essential regulators of the mitotic and meiotic cell cycles in eukaryotes [1.1.2, 1.4.1]. Aurora A (AURKA) primarily localizes to centrosomes and spindle poles, where it facilitates centrosome maturation and bipolar spindle assembly [1.1.1, 1.4.4]. Aurora B (AURKB) is a key component of the chromosomal passenger complex (CPC) and is responsible for chromosome alignment, the spindle assembly checkpoint, and cytokinesis [1.1.2, 1.2.2]. Aurora C (AURKC) is mainly expressed in germ cells and cooperates with Aurora B to regulate chromosome dynamics during meiosis and early embryonic mitosis [1.1.1, 1.1.2]. These kinases are frequently overexpressed or amplified in a wide range of human cancers, including leukemias and solid tumors, where they contribute to genetic instability and uncontrolled cell proliferation [1.1.3, 1.2.2]. Consequently, they have become significant therapeutic targets, with various small-molecule inhibitors developed to induce mitotic arrest and apoptosis [1.2.1, 1.2.4]. While several inhibitors have reached clinical trials, their development has been complicated by dose-limiting toxicities such as neutropenia and limited efficacy as monotherapy in solid tumors [1.2.3, 1.3.1].

Other names

Aurora A / Aurora B / Aurora CAurora kinase AAurora kinase BAurora kinase CAURKAAURKBAURKCSTK15STK12STK13AIK1AIK2AIK3ARK1ARK2ARK3BTAKAIM1Aurora 1Aurora 2Aurora 3

Aurora kinase inhibitors are ATP-competitive small molecules that bind to the catalytic domain of Aurora A, B, or C [1.2.1, 1.2.2]. Inhibition of Aurora A disrupts centrosome separation and spindle assembly, leading to a transient mitotic arrest and subsequent apoptosis [1.1.4, 1.2.3]. Inhibition of Aurora B prevents proper chromosome alignment and cytokinesis, resulting in polyploidy (cells with >4N DNA content) and eventual cell death [1.2.1, 1.2.3]. Pan-Aurora inhibitors combine these effects to achieve broad antineoplastic activity [1.2.1].