Abstract
Aurora kinases represent one of the emerging targets in oncology drug discovery. These kinases play important role in centrosome maturation, chromosome separation and cytokinesis. They are overexpressed in a broad range of tumor cell lines and human primary tumors; thus, their inhibition may open up new opportunities to develop novel anti-cancer agents. A range of potent small molecule inhibitors of Aurora kinases have been identified and found to have antitumor activity. Some of these agents are undergoing evaluation in clinical trials. Most synthetic Aurora kinase inhibitors are ATP-competitive, which makes selectivity a potential problem. However, despite the high sequence similarity in the ATPbinding pocket, several compounds are very specific in their targets. The ability of the inhibitors to extend their binding to regions adjacent to the ATP pocket, including the hydrophobic back pocket, contributes to the selectivity, since structural differences can be found in these regions. A common structural feature of the inhibitors is a planar heterocyclic ring system able to occupy the adenino-binding region and to mimic the adenine-kinase interactions, by making backbone hydrogen bond interactions, but also by extensive hydrophobic contacts within this part of the pocket. In this review we would like to analyse the main inhibitors, focusing on chemical structures, SAR and biological properties. The specific targeting of these kinases could result in highly active drugs with minimal collateral host toxicity. Moreover, the combination of Aurora inhibitors with other chemotherapeutic agents may open new opportunities in cancer chemotherapy.
Keywords: Aurora kinase, cell cycle, SAR, antitumor activity, ATP-competitive inhibitor
Current Medicinal Chemistry
Title: Small Molecule Aurora Kinases Inhibitors
Volume: 16 Issue: 16
Author(s): Laura Garuti, Marinella Roberti and Giovanni Bottegoni
Affiliation:
Keywords: Aurora kinase, cell cycle, SAR, antitumor activity, ATP-competitive inhibitor
Abstract: Aurora kinases represent one of the emerging targets in oncology drug discovery. These kinases play important role in centrosome maturation, chromosome separation and cytokinesis. They are overexpressed in a broad range of tumor cell lines and human primary tumors; thus, their inhibition may open up new opportunities to develop novel anti-cancer agents. A range of potent small molecule inhibitors of Aurora kinases have been identified and found to have antitumor activity. Some of these agents are undergoing evaluation in clinical trials. Most synthetic Aurora kinase inhibitors are ATP-competitive, which makes selectivity a potential problem. However, despite the high sequence similarity in the ATPbinding pocket, several compounds are very specific in their targets. The ability of the inhibitors to extend their binding to regions adjacent to the ATP pocket, including the hydrophobic back pocket, contributes to the selectivity, since structural differences can be found in these regions. A common structural feature of the inhibitors is a planar heterocyclic ring system able to occupy the adenino-binding region and to mimic the adenine-kinase interactions, by making backbone hydrogen bond interactions, but also by extensive hydrophobic contacts within this part of the pocket. In this review we would like to analyse the main inhibitors, focusing on chemical structures, SAR and biological properties. The specific targeting of these kinases could result in highly active drugs with minimal collateral host toxicity. Moreover, the combination of Aurora inhibitors with other chemotherapeutic agents may open new opportunities in cancer chemotherapy.
Export Options
About this article
Cite this article as:
Garuti Laura, Roberti Marinella and Bottegoni Giovanni, Small Molecule Aurora Kinases Inhibitors, Current Medicinal Chemistry 2009; 16 (16) . https://dx.doi.org/10.2174/092986709788682227
DOI https://dx.doi.org/10.2174/092986709788682227 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the Treatment of Chronic Inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more

- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Cytokine/Antibody Complexes: An Emerging Class of Immunostimulants
Current Pharmaceutical Design Fighting Tumor Cell Survival: Advances in the Design and Evaluation of Pim Inhibitors
Current Medicinal Chemistry Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection
Current Cancer Drug Targets Biotechnological Production of Taxol and Related Taxoids: Current State and Prospects
Anti-Cancer Agents in Medicinal Chemistry Notch-Associated MicroRNAs in Cancer
Current Drug Targets Antipyretic Medicinal Plants, Phytocompounds, and Green Nanoparticles: An Updated Review
Current Pharmaceutical Biotechnology Review on Documented Medicinal Plants used for the Treatment of Cancer
Current Traditional Medicine Anti-Cancer Role of Dendrosomal Nano Solanine in Chronic Myelogenous Leukemia Cell Line through Attenuation of PI3K/AKT/mTOR Signaling Pathway and Inhibition of hTERT Expression
Current Molecular Pharmacology Progress in the Development of Bestatin Analogues as Aminopeptidases Inhibitors
Current Medicinal Chemistry A Review on Synthesis, Anticancer and Antiviral Potentials of Pyrimidine Derivatives
Current Bioactive Compounds The Inhibitory Effect of Cyclosporine A and Prednisolone on Both Cytotoxic CD8+ T Cells and CD4+CD25+ Regulatory T Cells
Current Signal Transduction Therapy Targeting the Ubiquitin Proteasome System: Beyond Proteasome Inhibition
Current Pharmaceutical Design Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Cytotoxicity and Target Modulation in Pediatric Solid Tumors by the Proteasome Inhibitor Carfilzomib
Current Cancer Drug Targets An Overview of Innovations in Analysis and Beneficial Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry Src Family Kinases: Potential Targets for the Treatment of Human Cancer and Leukemia
Current Pharmaceutical Design Role of Genetics and Epigenetics in Mucosal, Uveal, and Cutaneous Melanomagenesis
Anti-Cancer Agents in Medicinal Chemistry The Role of Tumor Suppressor DLC-1: Far From Clear
Anti-Cancer Agents in Medicinal Chemistry Small Molecules in Cancer Therapy: Cytotoxics and Molecularly Targeted Agents
Current Signal Transduction Therapy Tumoral Drug Metabolism: Perspectives and Therapeutic Implications
Current Drug Metabolism