Abstract
The clinical success of the Bcr-Abl tyrosine kinase inhibitor Gleevec® and the recent clinical approval of a number of small molecule drugs that target protein kinases have intensified the search for novel protein kinase inhibitors. Since most small molecule kinase inhibitors target the highly conserved ATP-binding pocket of this enzyme family, the target selectivity of these molecules is a major concern. Due to the large size of the human kinome, it is a formidable challenge to determine the absolute specificity of a given protein kinase inhibitor, but recent technological developments have made substantial progress in achieving this goal. This review summarizes some of the most recent experimental techniques that have been developed for the determination of protein kinase inhibitor selectivity. Special emphasis is placed on the results of these screens and the general insights that they provide into kinase inhibitor target selectivity.
Keywords: ATP-binding cleft, mitogen activated protein kinase kinase, Affinity chromatography, Purvalanol B, yeast 2-hybrid assay
Combinatorial Chemistry & High Throughput Screening
Title: Chemical Genomic and Proteomic Methods for Determining Kinase Inhibitor Selectivity
Volume: 10 Issue: 8
Author(s): Ratika Krishnamurty and Dustin J. Maly
Affiliation:
Keywords: ATP-binding cleft, mitogen activated protein kinase kinase, Affinity chromatography, Purvalanol B, yeast 2-hybrid assay
Abstract: The clinical success of the Bcr-Abl tyrosine kinase inhibitor Gleevec® and the recent clinical approval of a number of small molecule drugs that target protein kinases have intensified the search for novel protein kinase inhibitors. Since most small molecule kinase inhibitors target the highly conserved ATP-binding pocket of this enzyme family, the target selectivity of these molecules is a major concern. Due to the large size of the human kinome, it is a formidable challenge to determine the absolute specificity of a given protein kinase inhibitor, but recent technological developments have made substantial progress in achieving this goal. This review summarizes some of the most recent experimental techniques that have been developed for the determination of protein kinase inhibitor selectivity. Special emphasis is placed on the results of these screens and the general insights that they provide into kinase inhibitor target selectivity.
Export Options
About this article
Cite this article as:
Krishnamurty Ratika and Maly J. Dustin, Chemical Genomic and Proteomic Methods for Determining Kinase Inhibitor Selectivity, Combinatorial Chemistry & High Throughput Screening 2007; 10 (8) . https://dx.doi.org/10.2174/138620707782507368
DOI https://dx.doi.org/10.2174/138620707782507368 |
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
-
MicroRNAs as Main Players in the Pathogenesis of Chronic Lymphocytic Leukemia
MicroRNA Knemometry for Assessment of Growth Suppressive Effects of Exogenous Glucocorticoids
Current Pediatric Reviews Bamboo a Supplement to Human Health: A Comprehensive Review on its Ethnopharmacology, Phytochemistry, and Pharmacological Activity
The Natural Products Journal Proteolytic Cleavage of Notch: “HIT and RUN”
Current Molecular Medicine Design, Preparation and Characterization of Modular Squalene-based Nanosystems for Controlled Drug Release
Current Topics in Medicinal Chemistry Synergistic Activities of a Silver(I) Glutamic Acid Complex and Reactive Oxygen Species (ROS): A Novel Antimicrobial and Chemotherapeutic Agent
Current Medicinal Chemistry Tyrosine Kinase Inhibitors
Current Cancer Drug Targets Antineoplastic Chemotherapy Induced QTc Prolongation
Current Drug Safety Pathways Related to the Anti-Cancer Effects of Metabolites Derived from Cerrado Biome Native Plants: An Update and Bioinformatics Analysis on Oral Squamous Cell Carcinoma
Protein & Peptide Letters Targeted Drug Delivery: Trends and Perspectives
Current Drug Delivery Overview of Tumor-Associated Antigens (TAAs) as Potential Therapeutic Targets for Prostate Cancer Therapy
Current Cancer Therapy Reviews Metastatic Breast Cancer, Organotropism and Therapeutics: A Review
Current Cancer Drug Targets Respiratory Stem Cells and Progenitors: Overview, Derivation, Differentiation, Carcinogenesis, Regeneration and Therapeutic Application
Current Stem Cell Research & Therapy Therapeutic Antibodies
Current Molecular Medicine Isoenzyme Selective Phosphoinositide 3-Kinase Inhibition: What do the Stones Kill?
Current Signal Transduction Therapy Withdrawal Notice: Role, Significance and Association of microRNA-10a/b in Physiology of Cancer
MicroRNA Privileged Scaffolds Targeting Bromodomain-containing Protein 4
Current Topics in Medicinal Chemistry Newly Identified Tumor Antigens as Promising Cancer Vaccine Targets for Malignant Melanoma Treatment
Current Topics in Medicinal Chemistry Innovative Cell Therapy in the Treatment of Serious Adverse Events Related to Both Chemo-Radiotherapy Protocol and Acute Myeloid Leukemia Syndrome: The Infusion of Mesenchymal Stem Cells Post-Treatment Reduces Hematopoietic Toxicity and Promotes Hematopoietic Reconstitution
Current Pharmaceutical Biotechnology Metaboloepigenetics: The Emerging Network in Stem Cell Homeostasis Regulation
Current Stem Cell Research & Therapy