Abstract
The Src family of non-transmembrane protein kinases is comprised of eleven homologous members in mammals. Together, these kinases regulate a wide variety of cellular processes including cell survival, proliferation, differentiation, and motility. One member of this family, Lck, plays a pivotal role in T-cell signaling. Inhibition of Lck with small molecules has significant potential for therapeutic immunosuppression and treatment of diseases such as rheumatoid arthritis and asthma. Critical for successful clinical use of any Lck inhibitor is high specificity for Lck as inhibition of other members of the Src kinase family may result in unwanted side effects. In this review we provide an overview of the various synthetic compounds currently under investigation as Lck-specific inhibitors. In addition we provide an analysis of the properties of these compounds that account for the specificity required for the inhibition of one of eleven highly similar kinases.
Keywords: Lck, Src, kinase, specificity, inhibitor, A-770041, BMS-243117, pyrrolopyrimidine
Mini-Reviews in Medicinal Chemistry
Title: Small Molecule Inhibitors of Lck: The Search for Specificity within a Kinase Family
Volume: 8 Issue: 6
Author(s): Malcolm A. Meyn III and Thomas E. Smithgall
Affiliation:
Keywords: Lck, Src, kinase, specificity, inhibitor, A-770041, BMS-243117, pyrrolopyrimidine
Abstract: The Src family of non-transmembrane protein kinases is comprised of eleven homologous members in mammals. Together, these kinases regulate a wide variety of cellular processes including cell survival, proliferation, differentiation, and motility. One member of this family, Lck, plays a pivotal role in T-cell signaling. Inhibition of Lck with small molecules has significant potential for therapeutic immunosuppression and treatment of diseases such as rheumatoid arthritis and asthma. Critical for successful clinical use of any Lck inhibitor is high specificity for Lck as inhibition of other members of the Src kinase family may result in unwanted side effects. In this review we provide an overview of the various synthetic compounds currently under investigation as Lck-specific inhibitors. In addition we provide an analysis of the properties of these compounds that account for the specificity required for the inhibition of one of eleven highly similar kinases.
Export Options
About this article
Cite this article as:
Meyn III A. Malcolm and Smithgall E. Thomas, Small Molecule Inhibitors of Lck: The Search for Specificity within a Kinase Family, Mini-Reviews in Medicinal Chemistry 2008; 8 (6) . https://dx.doi.org/10.2174/138955708784534454
DOI https://dx.doi.org/10.2174/138955708784534454 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
-
Essential Fatty Acids - A Review
Current Pharmaceutical Biotechnology Editorial (Thematic Issue: Rheumatology: An Evolutionary force in Biologics)
Current Pharmaceutical Design Quantum Dot-Based Nanoprobes for In Vivo Targeted Imaging
Current Molecular Medicine The Therapeutic Potential of ADAM15
Current Pharmaceutical Design Preclinical Profile of Bacopasides From Bacopa monnieri (BM) As An Emerging Class of Therapeutics for Management of Chronic Pains
Current Medicinal Chemistry Omega – 3 Fatty Acids as Pharmacotherapeutics in Psoriasis: Current Status and Scope of Nanomedicine in its Effective Delivery
Current Drug Targets Cartilage Oligomeric Matrix Protein: Matricellular and Matricrine Signaling in Cardiovascular Homeostasis and Disease
Current Vascular Pharmacology Neurological Effects of SARS-CoV-2 and Neurotoxicity of Antiviral Drugs Against COVID-19
Mini-Reviews in Medicinal Chemistry Monocyte Cyclooxygenase-2 Activity: A New Therapeutic Target for Atherosclerosis?
Current Drug Targets - Cardiovascular & Hematological Disorders Using an Ancient Tool for Igniting and Propagating Immune Tolerance: IDO as an Inducer and Amplifier of Regulatory T Cell Functions
Current Medicinal Chemistry A Proteomics Study of the Subacute Toxicity of Rat Brain after Long- Term Exposure of <i>Gelsemium elegans</i>
Current Molecular Pharmacology Extracts of Bacopa monnieri (L) Pennell Down-Regulate the Expression of Leukotriene C<sub>4</sub> Synthase mRNA in HL-60 Cells and Suppress OVAInduced Inflammation in BALB/c Mice
Current Bioactive Compounds Alternative Splicing: A Promising Target for Pharmaceutical Inhibition of Pathological Angiogenesis?
Current Pharmaceutical Design Circulating Osteoclast Precursors: A Mechanism and a Marker of Erosive Arthritis
Current Rheumatology Reviews Repositioning Drugs for Rare Immune Diseases: Hopes and Challenges for a Precision Medicine
Current Medicinal Chemistry Effect of Alpha-1-Acid Glycoprotein Binding on Pharmacokinetics and Pharmacodynamics
Current Drug Metabolism HLA-G Molecule
Current Pharmaceutical Design Corticotropin Releasing Factor (CRF) Peptide Family and their Receptors: Divergent Actions Influencing Human Physiology
Current Genomics Processed Foods, Dysbiosis, Systemic Inflammation, and Poor Health
Current Nutrition & Food Science Preface [Hot Topic: Perspective on VLA-4 Antagonists (Guest Editor: Jefferson W. Tilley)]
Current Topics in Medicinal Chemistry