Abstract
Small molecule inhibition of protein kinases in the treatment of significant diseases such as cancer, Alzheimers disease, diabetes, and rheumatoid arthritis has attracted significant attention over the past two decades and has clearly become one of the most significant challenges for drug discovery in the 21st century. While the recent identification of 518 different kinases in the human genome has offered a wealth of opportunities for drug intervention in the treatment of these diseases, it has also created a daunting challenge with respect to selective kinase inhibition as a viable strategy in target-based drug design. Over the past decade, the design and development of a small molecule that selectively inhibits the p38 mitogen activated protein (MAP) kinase has clearly emerged as one of these challenges within the industry. This review will focus on the comparison of the x-ray crystal structures and binding models of the most recent p38 inhibitor-enzyme complexes and the identification of the structural elements and interactions that may be important in providing inhibitor potency and selectivity toward the p38 MAP kinase.
Keywords: pharmacophores, extracellular regulated kinases, atp binding pocket, pyrimidylimidazoles, x-ray co-crystallization, diaryl ketones
Current Topics in Medicinal Chemistry
Title: Structural Comparison of p38 Inhibitor-Protein Complexes: A Review of Recent p38 Inhibitors Having Unique Binding Interactions
Volume: 5 Issue: 10
Author(s): Stephen T. Wrobleski and Arthur M. Doweyko
Affiliation:
Keywords: pharmacophores, extracellular regulated kinases, atp binding pocket, pyrimidylimidazoles, x-ray co-crystallization, diaryl ketones
Abstract: Small molecule inhibition of protein kinases in the treatment of significant diseases such as cancer, Alzheimers disease, diabetes, and rheumatoid arthritis has attracted significant attention over the past two decades and has clearly become one of the most significant challenges for drug discovery in the 21st century. While the recent identification of 518 different kinases in the human genome has offered a wealth of opportunities for drug intervention in the treatment of these diseases, it has also created a daunting challenge with respect to selective kinase inhibition as a viable strategy in target-based drug design. Over the past decade, the design and development of a small molecule that selectively inhibits the p38 mitogen activated protein (MAP) kinase has clearly emerged as one of these challenges within the industry. This review will focus on the comparison of the x-ray crystal structures and binding models of the most recent p38 inhibitor-enzyme complexes and the identification of the structural elements and interactions that may be important in providing inhibitor potency and selectivity toward the p38 MAP kinase.
Export Options
About this article
Cite this article as:
Wrobleski T. Stephen and Doweyko M. Arthur, Structural Comparison of p38 Inhibitor-Protein Complexes: A Review of Recent p38 Inhibitors Having Unique Binding Interactions, Current Topics in Medicinal Chemistry 2005; 5 (10) . https://dx.doi.org/10.2174/1568026054985894
DOI https://dx.doi.org/10.2174/1568026054985894 |
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
-
Determinants of Left Ventricular Hypertrophy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Imaging of Visceral Adipose Tissue: An Emerging Diagnostic Tool and Therapeutic Target
Current Drug Targets - Cardiovascular & Hematological Disorders Repositioning of Drugs in Cardiometabolic Disorders: Importance and Current Scenario
Current Topics in Medicinal Chemistry Potential Therapeutic Effects of Na+/Ca2+ Exchanger Inhibition in Cardiac Diseases
Current Medicinal Chemistry Novel Strategies for the Detection of Systolic and Diastolic Heart Failure
Current Cardiology Reviews New Perspective Therapy of Breast Cancer Based on Selective Dopamine Receptor D2 Agonist and Antagonist Effects on MCF-7 Cell Line
Recent Patents on Anti-Cancer Drug Discovery Tetracyclic Triterpenoids in Herbal Medicines and their Activities in Diabetes and its Complications
Current Topics in Medicinal Chemistry Prognostic Relevance of Metabolic Approach in Patients with Heart Failure
Current Pharmaceutical Design Selenium Containing Compounds from Poison to Drug Candidates: A Review on the GPx-like Activity
Current Chemical Biology Drug Repositioning: A Smart Approach for Combating SARS-CoV-2
Anti-Infective Agents Circulatory Syndrome: An Evolution of the Metabolic Syndrome Concept!
Current Cardiology Reviews Characterizing the Bi-Subunit Type IB DNA Topoisomerase of Leishmania Parasites; a Novel Scenario for Drug Intervention in Trypanosomatids
Current Drug Targets Hutchinson-Gilford Progeria Syndrome: An Overview of the Molecular Mechanism, Pathophysiology and Therapeutic Approach
Current Gene Therapy Gene Clusters, Molecular Evolution and Disease: A Speculation
Current Genomics Anti-inflammatory Treatment of Acute Coronary Syndromes
Current Pharmaceutical Design Endothelial Expression of MHC Class II Molecules in Autoimmune Disease
Current Pharmaceutical Design Endoplasmic Reticulum Stress in Arterial Smooth Muscle Cells: A Novel Regulator of Vascular Disease
Current Cardiology Reviews Mitochondrial Biogenesis: Regulation By Endogenous Gases During Inflammation and Organ Stress
Current Pharmaceutical Design Pathophysiological and Clinical Aspects of Iron Chelation Therapy in MDS
Current Pharmaceutical Design Chelating Agents for Metal Intoxication
Current Medicinal Chemistry