Abstract
The pivotal role of kinases in signal transduction and cellular regulation has lent them considerable appeal as pharmacological targets across a broad spectrum of pathologies. Since the discovery that the v-Src oncogene encoded a protein kinase in 1978, kinases have remained a focus of research for pharmaceutical laboratories and academic groups alike. Many have sought to develop orally available low molecular weight synthetic kinase modulators (predominantly inhibitors) and thus capitalize on the links between aberrant regulation and disease. This interest in kinases as drug targets was fueled in recent years by the success of several kinase inhibitors in the clinic, primarily Gleevec for the treatment of chronic myelogenous leukemia and Iressa for the treatment of advanced non-small cell lung cancer. This review focuses on the development of small molecule drugs, most of them binding in or close to the ATP binding pocket. After some general considerations regarding the selection of a particular kinase for drug discovery, we will discuss the encouraging lessons learned from some of the kinase inhibitors currently in various stages of development. The majority of this review is dedicated to a detailed description and discussion of the various assay formats currently being employed for high throughput screening.
Keywords: kinase, high throughput screening
Combinatorial Chemistry & High Throughput Screening
Title: High Throughput Screening for Protein Kinase Inhibitors
Volume: 8 Issue: 2
Author(s): Holger Wesche, Shou-Hua Xiao and Steve W. Young
Affiliation:
Keywords: kinase, high throughput screening
Abstract: The pivotal role of kinases in signal transduction and cellular regulation has lent them considerable appeal as pharmacological targets across a broad spectrum of pathologies. Since the discovery that the v-Src oncogene encoded a protein kinase in 1978, kinases have remained a focus of research for pharmaceutical laboratories and academic groups alike. Many have sought to develop orally available low molecular weight synthetic kinase modulators (predominantly inhibitors) and thus capitalize on the links between aberrant regulation and disease. This interest in kinases as drug targets was fueled in recent years by the success of several kinase inhibitors in the clinic, primarily Gleevec for the treatment of chronic myelogenous leukemia and Iressa for the treatment of advanced non-small cell lung cancer. This review focuses on the development of small molecule drugs, most of them binding in or close to the ATP binding pocket. After some general considerations regarding the selection of a particular kinase for drug discovery, we will discuss the encouraging lessons learned from some of the kinase inhibitors currently in various stages of development. The majority of this review is dedicated to a detailed description and discussion of the various assay formats currently being employed for high throughput screening.
Export Options
About this article
Cite this article as:
Wesche Holger, Xiao Shou-Hua and Young W. Steve, High Throughput Screening for Protein Kinase Inhibitors, Combinatorial Chemistry & High Throughput Screening 2005; 8 (2) . https://dx.doi.org/10.2174/1386207053258514
DOI https://dx.doi.org/10.2174/1386207053258514 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
Integrating Network Pharmacology and Traditional Medicine: A New Perspective in Drug Mechanism Research
Network pharmacology is a network construction and network topology analysis strategy that combines pharmacology and pharmacodynamics. In recent years, network pharmacology has emerged as a powerful tool that can be integrated with pharmacology. Natural products commonly function in multicomponent, multitarget, and multipathway systems. Some examples encompass Ayurveda, traditional Chinese medicines ...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
Related Articles
-
Ionic Liquids for Topical Delivery in Cancer
Current Medicinal Chemistry Identification of Tumor Targeting Agents by Phage Display
Medicinal Chemistry Reviews - Online (Discontinued) Application and Interpretation of Genome-Wide Association (GWA) Studies for Informing Pharmacogenomic Research - Examples from the Field of Age-Related Macular Degeneration
Current Molecular Medicine Can PET Imaging Facilitate Optimization of Cancer Therapies?
Current Pharmaceutical Design The Potency of Refined Mouse Models: Implications for Clinical Trials
Current Cancer Therapy Reviews In Vivo Tumor Secretion Probing Via Ultrafiltration and Tissue Chamber:Implication for Anti-Cancer Drugs Targeting Secretome
Recent Patents on Anti-Cancer Drug Discovery Editorial
Current Cancer Therapy Reviews Self-Assembled Micelles of Amphiphilic PEGylated Drugs for Cancer Treatment
Current Drug Targets Current Protein-based Anti-angiogenic Therapeutics
Mini-Reviews in Medicinal Chemistry Biological Activities of Eco-Friendly Synthesized Hantzsch Adducts
Medicinal Chemistry Imaging Primary Brain Tumors by Single-Photon Emission Computerized Tomography (SPECT) with Technetium-99m Sestamibi (MIBI) and Tetrofosmin
Current Medical Imaging Recent Developments in Protein and Cell-Targeted Aptamer Selection and Applications
Current Medicinal Chemistry A Review of Mechanisms of Circumvention and Modulation of Chemotherapeutic Drug Resistance
Current Cancer Drug Targets The Protein-Protein Interaction-Mediated Inactivation of PTEN
Current Molecular Medicine Advances in Tumor Targeted Liposomes
Current Molecular Medicine Molecular Targets in Gastrointestinal Stromal Tumors (GIST) Therapy
Current Cancer Drug Targets Autoantibody Profiles as Biomarkers for Response to Therapy and Early Detection of Cancer
Current Cancer Therapy Reviews Secretory Leukocyte Protease Inhibitor: More than Just A Protease Inhibitor
Current Immunology Reviews (Discontinued) Antitumor Effect of Cycle Inhibiting Factor Expression in Colon Cancer <i>via Salmonella</i> VNP20009
Anti-Cancer Agents in Medicinal Chemistry Exosomes: A Promising Factor Involved in Cancer Hypoxic Microenvironments
Current Medicinal Chemistry