Abstract
The p38 mitogen activated protein (MAP) kinase is an integral enzyme involved in the production of a wide variety of pro-inflammatory cytokines from various cell types. The identification of this kinase and of the diaryl imidazole containing inhibitor, SB203580, initiated an intense discovery effort in this field. Numerous inhibitors were subsequently produced containing replacements for the imidazole, as well as some of the pharmacophores attached to it. During this time many other classes of potent p38 inhibitors emerged containing scaffolds and binding components not found in the diaryl imidazole group. This review summarizes nine of those classes. At least one of these classes requires the kinase to undergo reorganization prior to binding. From this diverse set of inhibitors four compounds have been reported advancing into human clinical trials.
Keywords: kinase inhibition, anti-cancer agents, purine-derived compounds, cell cycle, solid phase synthesis, biological activity
Current Topics in Medicinal Chemistry
Title: The Non-Diaryl Heterocycle Classes of p38 MAP Kinase Inhibitors
Volume: 2 Issue: 9
Author(s): Pier F. Cirillo, Christopher Pargellis and John Regan
Affiliation:
Keywords: kinase inhibition, anti-cancer agents, purine-derived compounds, cell cycle, solid phase synthesis, biological activity
Abstract: The p38 mitogen activated protein (MAP) kinase is an integral enzyme involved in the production of a wide variety of pro-inflammatory cytokines from various cell types. The identification of this kinase and of the diaryl imidazole containing inhibitor, SB203580, initiated an intense discovery effort in this field. Numerous inhibitors were subsequently produced containing replacements for the imidazole, as well as some of the pharmacophores attached to it. During this time many other classes of potent p38 inhibitors emerged containing scaffolds and binding components not found in the diaryl imidazole group. This review summarizes nine of those classes. At least one of these classes requires the kinase to undergo reorganization prior to binding. From this diverse set of inhibitors four compounds have been reported advancing into human clinical trials.
Export Options
About this article
Cite this article as:
Cirillo F. Pier, Pargellis Christopher and Regan John, The Non-Diaryl Heterocycle Classes of p38 MAP Kinase Inhibitors, Current Topics in Medicinal Chemistry 2002; 2 (9) . https://dx.doi.org/10.2174/1568026023393390
DOI https://dx.doi.org/10.2174/1568026023393390 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Anti-platelet Drug-loaded Targeted Technologies for the Effective Treatment of Atherothrombosis
Current Drug Targets Rationale for the Development of Cholinesterase Inhibitors as Anti- Alzheimer Agents
Current Pharmaceutical Design Potent Inhibitory Effects of p7 Inhibitors on Genotype 4 HCV-infected Peripheral Blood Mononuclear Cells
Recent Patents on Biomarkers CYP24A1 as a Potential Target for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Hypersensitivity to Febuxostat in a Patient with a Previous Allopurinolinduced Steven-Johnson Syndrome: A Case Report of Treatment with a Slow Desensitization Protocol
Endocrine, Metabolic & Immune Disorders - Drug Targets Modification of Decoy Oligodeoxynucleotides to Achieve the Stability and Therapeutic Efficacy
Current Topics in Medicinal Chemistry Gastric Ulcerogenic and Healing Impairment Actions of Alendronate, A Nitrogen- Containing Bisphosphonate - Prophylactic Effects of Rebamipide
Current Pharmaceutical Design New Anticancer Drugs from Marine Cyanobacteria
Current Drug Targets Neuroprotective Potential and Underlying Pharmacological Mechanism of Carvacrol for Alzheimer’s and Parkinson’s Diseases
Current Neuropharmacology Role of Dietary Fiber in Formation and Prevention of Small Intestinal Ulcers Induced by Nonsteroidal Anti-Inflammatory Drug
Current Pharmaceutical Design Current Therapeutic Strategies and Future Perspectives for the Prevention of Arterial Thromboembolism: Focus on Atrial Fibrillation
Current Pharmaceutical Design Oncolytic Virotherapy for Breast Cancer Treatment
Current Gene Therapy Drug Nanocarriers and Functional Nanoparticles: Applications in Cancer Therapy
Current Drug Delivery Effects of Melatonin on Peripheral Nerve Regeneration
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Repositioning Drugs for Rare Immune Diseases: Hopes and Challenges for a Precision Medicine
Current Medicinal Chemistry The Role of Chemokines in the Pathogenesis of Rheumatoid Arthritis
Current Rheumatology Reviews Betaxolol Hydrochloride Loaded Chitosan Nanoparticles for Ocular Delivery and their Anti-glaucoma Efficacy
Current Drug Delivery Role and Pharmacogenomics of TNF-α in Asthma
Mini-Reviews in Medicinal Chemistry Risperidone Rechallenge for Marked Liver Function Test Abnormalities in an Autistic Child
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Immune Deviation Strategies in the Therapy of Psoriasis
Current Drug Targets - Inflammation & Allergy