Abstract
Mitogen-activated protein kinase p38 is a serine/threonine kinase originally isolated from lipopolysaccharide (LPS) stimulated monocytes. There are four isoforms p38α, p38β, p38γ, and p38δ. The most thoroughly studied isoform is p38α, whose activation has been observed in many hematopoietic and nonhematopoietic cell types upon appropriate stimuli. Subsequently, p38α kinase has been shown to be involved in the biosynthesis of TNFα and IL-1β at the translational and transcriptional level. MAP kinase p38agr; represents a point of convergence for multiple signaling processes that are activated in inflammation and thus a key potential target for the modulation of cytokine production. The discovery and publication of p38α and the pyridinyl-imidazole inhibitor initiated a huge effort by many companies to develop p38α inhibitors as potential treatment for inflammatory diseases. Herein we provide a brief overview of recent reported clinical results for AMG 548, BIRB 796, VX 702, SCIO 469, and SCIO 323. However, our focus will be on the binding modes of these inhibitors and other p38 inhibitors in the recent literature.
Keywords: p38 inhibitors, map kinase, tnfα, il-1β, dgf in, dgf out, amg 548, birb 796, scio 469
Current Medicinal Chemistry
Title: MAP Kinase p38Inhibitors: Clinical Results and an Intimate Look at Their Interactions with p38α Protein
Volume: 12 Issue: 25
Author(s): Matthew R. Lee and Celia Dominguez
Affiliation:
Keywords: p38 inhibitors, map kinase, tnfα, il-1β, dgf in, dgf out, amg 548, birb 796, scio 469
Abstract: Mitogen-activated protein kinase p38 is a serine/threonine kinase originally isolated from lipopolysaccharide (LPS) stimulated monocytes. There are four isoforms p38α, p38β, p38γ, and p38δ. The most thoroughly studied isoform is p38α, whose activation has been observed in many hematopoietic and nonhematopoietic cell types upon appropriate stimuli. Subsequently, p38α kinase has been shown to be involved in the biosynthesis of TNFα and IL-1β at the translational and transcriptional level. MAP kinase p38agr; represents a point of convergence for multiple signaling processes that are activated in inflammation and thus a key potential target for the modulation of cytokine production. The discovery and publication of p38α and the pyridinyl-imidazole inhibitor initiated a huge effort by many companies to develop p38α inhibitors as potential treatment for inflammatory diseases. Herein we provide a brief overview of recent reported clinical results for AMG 548, BIRB 796, VX 702, SCIO 469, and SCIO 323. However, our focus will be on the binding modes of these inhibitors and other p38 inhibitors in the recent literature.
Export Options
About this article
Cite this article as:
Lee R. Matthew and Dominguez Celia, MAP Kinase p38Inhibitors: Clinical Results and an Intimate Look at Their Interactions with p38α Protein, Current Medicinal Chemistry 2005; 12 (25) . https://dx.doi.org/10.2174/092986705774462914
DOI https://dx.doi.org/10.2174/092986705774462914 |
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
-
The Warburg Effect on Cancer Cells Survival: The Role of Sugar Starvation in Cancer Therapy
Current Reviews in Clinical and Experimental Pharmacology Meet Our Editorial Board Member
Endocrine, Metabolic & Immune Disorders - Drug Targets The Role of Diabetes Mellitus in Sexual and Reproductive Health: An Overview of Pathogenesis, Evaluation, and Management
Current Diabetes Reviews Role of Renin-Angiotensin System in Inflammation, Immunity and Aging
Current Pharmaceutical Design Clinical Studies with Paclitaxel - Eluting Stent Systems
Current Pharmaceutical Design Luteolin Regulates Macrophage Polarization via the PI3K/Akt Pathway to Inhibit the Apoptosis Stimulated by Angiotensin II
Current Pharmaceutical Biotechnology Scientific Evidence for the Treatment of Children with Irritable Bowel Syndrome
Current Pediatric Reviews Phase 1 Clinical Experience Using Intravenous Administration of PV701, an Oncolytic Newcastle Disease Virus
Current Cancer Drug Targets Orphan Nuclear Receptors, Excellent Targets of Drug Discovery
Combinatorial Chemistry & High Throughput Screening Preface [Hot Topic: Cytochrome P450 and Diseases: Implications in Drug Metabolism and Pathophysiology (Guest Editor: Vincent Pichette)]
Current Drug Metabolism Structure-Activity Relationship Analyses of Glycyrrhetinic Acid Derivatives as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Recent Developments to Improve the Efficacy of Cytotoxic Nucleoside Analogues
Recent Patents on Anti-Cancer Drug Discovery Antiangiogenic Therapy
Current Pharmaceutical Design Immunomodulating Properties of Macrolides: Animal and Human Studies
Current Medicinal Chemistry - Anti-Infective Agents CARING (CAncer Risk and INsulin analoGues): The Association of Diabetes Mellitus and Cancer Risk with Focus on Possible Determinants - A Systematic Review and a Meta-Analysis
Current Drug Safety Clinical Ritonavir and Lopinavir Hypersensitivity Confirmed by a Specific In Vitro Cellular Allergen Stimulation Test
Current HIV Research Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases
Current Medicinal Chemistry Prognostic Impact of Red Cell Distribution Width on the Development of Contrast-Induced Nephropathy, Major Adverse Cardiac Events, and Mortality in Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention
Current Cardiology Reviews VEGF Signal System: The Application of Antiangiogenesis
Current Medicinal Chemistry Antibacterial Function of the Human Cathelicidin-18 Peptide (LL-37) between Theory and Practice
Protein & Peptide Letters