Aurora Kinases and Potential Medical Applications of Aurora Kinase Inhibitors: A Review
نویسندگان
چکیده
Aurora kinases (AKs) represent a novel group of serine/threonine kinases. They were originally described in 1995 by David Glover in the course of studies of mutant alleles characterized with unusual spindle pole configuration in Drosophila melanogaster. Thus far, three AKs A, B, and C have been discovered in human healthy and neoplastic cells. Each one locates in different subcellular locations and they are all nuclear proteins. AKs are playing an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. Any inactivation of them can have catastrophic consequences on mitotic events of spindle formation, alignment of centrosomes and cytokinesis, resulting in apoptosis. Overexpression of AKs has been detected in diverse solid and hematological cancers and has been linked with a dismal prognosis. After discovery and identification of the first aurora kinase inhibitor (AKI) ZM447439 as a potential drug for targeted therapy in cancer treatment, approximately 30 AKIs have been introduced in cancer treatment.
منابع مشابه
Aurora kinases: structure, functions and their association with cancer.
BACKGROUND Aurora kinases are a recently discovered family of kinases (A, B & C) consisting of highly conserved serine\threonine protein kinases found to be involved in multiple mitotic events: regulation of spindle assembly checkpoint pathway, function of centrosomes and cytoskeleton, and cytokinesis. Aberrant expression of Aurora kinases may lead to cancer. For this reason the Aurora kinases ...
متن کاملAurora-A kinase inhibitor scaffolds and binding modes.
Aurora kinases (A-C) belong to the serine/threonine protein kinase family. In recent years, the constitutive or elevated expression of Aurora kinases has been found in cancer cells and oncogene transfected cells. In this review, we summarize the common binding modes of Aurora-A kinase inhibitors, the hot spot residues in the binding sites and the privileged inhibitor structures. Our review of t...
متن کاملAurora Kinase Inhibitors in Target Specific Cancer Treatment
Targeted therapy is one of the major treatment modalities in medical oncology. Targeted therapy aims to inhibit oncogenic pathways by interfering with target biomolecules. For this reason drug designers have focused on investigation of new targets in order to develop efficient cancer drugs [1]. Aurora kinases are important members of the serine/threonine kinases and three forms of the Aurora ki...
متن کاملAurora Kinases as Targets in Drug-Resistant Neuroblastoma Cells
Aurora kinase inhibitors displayed activity in pre-clinical neuroblastoma models. Here, we studied the effects of the pan-aurora kinase inhibitor tozasertib (VX680, MK-0457) and the aurora kinase inhibitor alisertib (MLN8237) that shows some specificity for aurora kinase A over aurora kinase B in a panel of neuroblastoma cell lines with acquired drug resistance. Both compounds displayed anti-ne...
متن کاملEditorial: Aurora Kinases: Classical Mitotic Roles, Non-Canonical Functions and Translational Views
Aurora kinases are key mitotic regulators that have also been associated with tumor development and progression. The interest on this highly conserved family of protein kinases has grown exponentially since they were discovered in the 1990s. Despite the steady increase in the number of laboratories involved and the consequent boost of the volume of research output during the last years, the stu...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 7 شماره
صفحات -
تاریخ انتشار 2015