Abstract
Control of NF-κB release through the inhibition of I & κB kinase β (IKKβ) has been identified as a potential target for the treatment of inflammatory and autoimmune diseases. To screen the small molecule compound library against IKKβ, a high throughput screening (HTS) campaign was carried out using immobilized metal affinity for phosphochemicals (IMAP)-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. Through serial optimization of assay conditions, the Z value was achieved at 0.88 from the pilot library screening of the most diverse 7,243 compounds with reconfirmation rate of 63%. The results from this HTS campaign identified three novel scaffolds for the prospective IKKβ inhibitor, such as 7-benzoyl-4-phenylcyclopenta [1,2] oxazine, 1-(thiophen or furan)-2,3- dihydroimidazo[1,5] pyridine and 2-phenyloxazolo [5,4] pyridine. Particularly, 7-benzoyl-4-phenylcyclopenta [1,2] oxazine derivatives presented potent inhibitory activity and selectivity for IKKβ. These findings suggest that the current TR-FRET assay system for IKKβ was successful to identify hits for novel IKKβ inhibitors as a robust, reproducible and sensitive HTS system.
Keywords: IκB kinase β, IKKβ inhibitor, time-resolved fluorescence resonance energy transfer.
Combinatorial Chemistry & High Throughput Screening
Title: Identification of Novel Scaffolds for IκB Kinase Beta Inhibitor via a High Throughput Screening TR-FRET Assay
Volume: 13 Issue: 9
Author(s): Kwang-Seok Oh, Sunghou Lee, Joong Kwon Choi and Byung Ho Lee
Affiliation:
Keywords: IκB kinase β, IKKβ inhibitor, time-resolved fluorescence resonance energy transfer.
Abstract: Control of NF-κB release through the inhibition of I & κB kinase β (IKKβ) has been identified as a potential target for the treatment of inflammatory and autoimmune diseases. To screen the small molecule compound library against IKKβ, a high throughput screening (HTS) campaign was carried out using immobilized metal affinity for phosphochemicals (IMAP)-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. Through serial optimization of assay conditions, the Z value was achieved at 0.88 from the pilot library screening of the most diverse 7,243 compounds with reconfirmation rate of 63%. The results from this HTS campaign identified three novel scaffolds for the prospective IKKβ inhibitor, such as 7-benzoyl-4-phenylcyclopenta [1,2] oxazine, 1-(thiophen or furan)-2,3- dihydroimidazo[1,5] pyridine and 2-phenyloxazolo [5,4] pyridine. Particularly, 7-benzoyl-4-phenylcyclopenta [1,2] oxazine derivatives presented potent inhibitory activity and selectivity for IKKβ. These findings suggest that the current TR-FRET assay system for IKKβ was successful to identify hits for novel IKKβ inhibitors as a robust, reproducible and sensitive HTS system.
Export Options
About this article
Cite this article as:
Oh Kwang-Seok, Lee Sunghou, Kwon Choi Joong and Ho Lee Byung, Identification of Novel Scaffolds for IκB Kinase Beta Inhibitor via a High Throughput Screening TR-FRET Assay, Combinatorial Chemistry & High Throughput Screening 2010; 13 (9) . https://dx.doi.org/10.2174/138620710792927367
DOI https://dx.doi.org/10.2174/138620710792927367 |
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
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...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
- 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
-
HSP60 as a Drug Target
Current Pharmaceutical Design Mesenchymal Stem Cells Induced In Vitro Generated Regulatory-T Cells: Potential Soldiers of Transplantation Biology
Current Biotechnology Application of Agents Against Interferon-Gamma-Dependent Chemokines in Immunotherapy
Letters in Drug Design & Discovery PKC-θ is a Drug Target for Prevention of T Cell-Mediated Autoimmunity and Allograft Rejection
Endocrine, Metabolic & Immune Disorders - Drug Targets The Rationale for Comparative Studies of Accelerated Atherosclerosis in Rheumatic Diseases
Current Vascular Pharmacology Targeting of Th1-Associated Chemokine Receptors CXCR3 and CCR5 as Therapeutic Strategy for Inflammatory Diseases
Mini-Reviews in Medicinal Chemistry Autoimmune Diseases and Atherosclerosis: The Inflammatory Connection
Current Immunology Reviews (Discontinued) Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors
Current Cardiology Reviews Therapeutic Approach to Multiple Sclerosis by Novel Oral Drugs
Recent Patents on Inflammation & Allergy Drug Discovery Manipulating Thymic Apoptosis for Future Therapy of Autoimmune Diseases
Current Pharmaceutical Design Chemokines as Drug Targets in Type 1 Diabetes
Endocrine, Metabolic & Immune Disorders - Drug Targets Modifying TNF alpha for Therapeutic Use A Perspective on the TNF Receptor System
Mini-Reviews in Medicinal Chemistry Cardiovascular Involvement in Pediatric Systemic Autoimmune Diseases: The Emerging Role of Noninvasive Cardiovascular Imaging
Inflammation & Allergy - Drug Targets (Discontinued) Recent Applications of Chemiluminescence Assays in Clinical Immunology
Mini-Reviews in Medicinal Chemistry The New Immunosuppression: Intervention at the Dendritic Cell-T-Cell Interface
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Molecular Characterization of the T Cell Repertoire Using Immuno-scope Analysis and its Possible Implementation in Clinical Practice
Current Molecular Medicine The Soluble CTLA-4 Receptor and its Emerging Role in Autoimmune Diseases
Current Immunology Reviews (Discontinued) Sphingolipids in Cell Signaling: Their Function as Receptor Ligands, Second Messengers, and Raft Constituents
Current Immunology Reviews (Discontinued) Naturally Arising CD25+CD4+ Regulatory T Cells in Maintaining Immunologic Self-Tolerance and Preventing Autoimmune Disease
Current Molecular Medicine Cell-free DNA: Characteristics, Detection and its Applications in Myocardial Infarction
Current Pharmaceutical Design