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
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
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from 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
-
Design, Development and Evaluation of Celecoxib-Loaded Microsponge-Based Topical Gel Formulation
Applied Clinical Research, Clinical Trials and Regulatory Affairs Immunoregulation Through 1,25-Dihydroxyvitamin D 3 and its Analogs
Current Drug Targets - Inflammation & Allergy Constrained Analogs of Osteogenic Peptides
Current Medicinal Chemistry Strategies to Control Human Lymphatic Filarial Infection: Tweaking Host’s Immune System
Current Topics in Medicinal Chemistry Novel Biomarkers Assessing the Calcium Deposition in Coronary Artery Disease
Current Medicinal Chemistry Inhibition of Tumor Angiogenesis by Antibodies, Synthetic Small Molecules and Natural Products
Current Medicinal Chemistry Humanized SCID Mice Models of SLE
Current Pharmaceutical Design TNF-Related Apoptosis-Inducing Ligand (TRAIL) as a Pro-Apoptotic Signal Transducer with Cancer Therapeutic Potential
Current Pharmaceutical Design Pharmacologically Targeting the Primary Defect and Downstream Pathology in Duchenne Muscular Dystrophy
Current Gene Therapy Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules
Current Medicinal Chemistry Regulation and Effect of Telomerase and Telomeric Length in Stem Cells
Current Stem Cell Research & Therapy Anti-Cancer Agent-Induced Nephrotoxicity
Anti-Cancer Agents in Medicinal Chemistry Biologic Agents for Treatment of Rheumatoid Arthritis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Soluble Epoxide Hydrolase, a Target with Multiple Opportunities for Cardiovascular Drug Discovery
Current Topics in Medicinal Chemistry Cell Therapies for IBD: What Works?
Current Drug Targets Lung Defence Mechanisms and Their Potential Role in the Prevention of Ventilator Associated Pneumonia
Current Respiratory Medicine Reviews Apolipoprotein E Derived Peptides Inhibit the Pro-Inflammatory Effect of Lysophosphatidylcholine
Protein & Peptide Letters Regulation of Ocular Immune Responses by Corneal Epithelium
Current Immunology Reviews (Discontinued) The Molecular Targets of Cannabinoids in the Treatment of Cancer and Inflammation
Current Pharmaceutical Design Recent Updates on Biological Activities of Oxadiazoles
Mini-Reviews in Medicinal Chemistry