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.
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http://dx.doi.org/10.14740/jocmr2295w | DOI Listing |
J Med Chem
January 2025
Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Simultaneous inhibition of the bromodomain and extra-terminal domain and Aurora kinases is a promising anticancer therapeutic strategy. Based on our previous study on BET-kinase dual inhibitors, we employed the molecular docking approach to design novel dual BET-Aurora kinase A inhibitors. Through several rounds of optimization and with the guidance of the solved cocrystal structure of BRD4 bound to inhibitor , we finally obtained a series of highly potent dual BET-Aurora kinase A inhibitors.
View Article and Find Full Text PDFBMC Oral Health
January 2025
Department of Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
Background: Aurora kinase A (AurkA) plays a vital role in mitosis and is therefore critical in tumors development and progression. There are a few studies on AurkA expression in salivary gland tumors. The aim of the present study was to evaluate the expression pattern of AurkA in the most common benign and malignant salivary gland tumors by immunohistochemistry.
View Article and Find Full Text PDFPLoS One
January 2025
Information School, The Wave, The University of Sheffield, Sheffield, United Kingdom.
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression level of the target genes in the cell. Breast cancer is responsible for the majority of cancer-related deaths among women globally. It has been proven that deregulated miRNAs may play an essential role in the progression of breast cancer.
View Article and Find Full Text PDFCell Death Dis
January 2025
Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia.
Polyploidy is a common outcome of chemotherapies, but there is conflicting evidence as to whether polyploidy is an adverse, benign or even favourable outcome. We show Aurora B kinase inhibitors efficiently promote polyploidy in many cell types, resulting in the cell cycle exit in RB and p53 functional cells, but hyper-polyploidy in cells with loss of RB and p53 function. These hyper-polyploid cells (>8n DNA content) are viable but have lost long-term proliferative potential in vitro and fail to form tumours in vivo.
View Article and Find Full Text PDFCell Chem Biol
January 2025
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.
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