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Aurora Kinase Inhibitors: The Dawn Of A New Approach To Cancer

LeadDiscovery
May 1, 2006
SKU: LD1330766

Abstract Table of Contents Related Reports

Cell cycle inhibitors represent a key approach to the treatment of cancer. Therapeutic agents have traditionally targeted early stages of the cell cycle (ie the G1/S phase checkpoint or the S phase) or mitotic spindle formation as exemplified by the alkaloids. Recently a new approach to cell cycle regulation has emerged with the identification of the Aurora kinase family. This family plays a role in later stages of the cell cycle from the G2/M check point all the way through to the mitotic checkpoint and late mitosis.

Aurora Kinase Inhibitors: The dawn of a new approach to cancer was written as a target evaluation/drug development update report. This analysis was intended to provide a framework for all organizations considering entry into this exciting field or those already in the field but who require competitive intelligence within the area. The report:

Introduces the Aurora kinases
Analyzes the proof of concept supporting the development of aurora kinase inhibitors for the treatment of cancer
Discusses mechanism of action
Evaluates drugs in development
Provides strategic guidance on kinase selectivity
Discusses the promise and risks of kinase inhibitors
Offers competitive intelligence discussing how Aurora kinase inhibitors would fit into the current oncology treatment area. The report compares this class with existing and emerging classes and evaluates the part that Aurora kinase inhibitors could play in the combinatorial approach to cancer

Our understanding of the Aurora kinase family and its role in cell division has advanced over recent years and the drug discovery community is now in a good position to judge the proof of concept supporting the development of Aurora kinase inhibitors.

1. Summary
2. Background
3. Eukaryotic Chromosome Packaging
4. HDAC: An Early History
5. Chromatin remodeling in transcriptional control
6. The Mammalian HDAC enzymes: The Class I HDACs; The Class II HDACs; The Class III HDACs
7. The HDACs and transcriptional silencing - molecular strategies for achieving transcriptional control: The histone code; HDAC complexes; Transcriptional consequences of HDAC inhibition; Regulation of transcription factor access; Non-histone (de)acetylation; Long-range repression; Kinetics of histone acetylation/deacetylation; Heterochromatin
8. HDAC:protein interactions: Multiprotein HDAC co-repressor complexes
9. Post-translational modifications in the control of HDAC activity: Phosphorylation/dephosphorylation; SUMOylation
10. Biological consequences of HDAC inhibition: Cell differentiation; Cell cycle arrest; Apoptosis; Cytoskeletal alterations; Angiogenesis
11: Progress in chemical development of HDAC inhibitors: The short-chain fatty acids; The hydroxamic acids; The amides; The epoxyketone-containing cyclic tetrapeptides; The non-epoxyketone-containing cyclic tetrapeptides; Miscellaneous structures
12. Profiles of HDAC inhibitors in clinical development: Phase II; Phase 1; Selected Preclinical
13. Strategic & Competitive Analysis: Issues surrounding the development of HDAC inhibitors; Competitive analysis; Apoptosis; Stimulators
14. Methodological considerations

Aurora Kinase Inhibitors: The Dawn Of A New Approach To Cancer

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