Abstract
FMS is the exclusive receptor tyrosine kinase for colony-stimulating factor-1 (CSF-1, also known as M-CSF), which regulates the survival, proliferation, differentiation, and function of macrophage lineage cells. Since CSF-1 is overexpressed in many tumors and at sites of inflammation, small molecule inhibitors of CSF-1 appear to offer an attractive strategy for reducing macrophage numbers associated with cancer as well as autoimmune and inflammatory disease, such as rheumatoid arthritis (RA). Numerous FMS inhibitors with structurally distinct chemotypes have been developed and exhibit potent in vitro activity, but only a limited number of compounds have progressed clinically due to poor selectivity. To date, only a handful of FMS inhibitors have been tested in models of metastatic bone disease and RA. This review will summarize the biology of FMS and its function in bone physiology, inflammation, immunity, and cancer. In addition, efforts directed towards identifying FMS-selective small molecule inhibitors as well as the advancement of non-selective inhibitors in the clinic will be highlighted. Furthermore, emerging monoclonal antibody-based therapeutic strategies specifically targeting M-CSF will be described.
Keywords: CSF-1R, FMS, M-CSF, colony stimulating factor-1, anti-inflammatory, macrophages
Current Topics in Medicinal Chemistry
Title: Colony-Stimulating Factor-1 Receptor Inhibitors for the Treatment of Cancer and Inflammatory Disease
Volume: 9 Issue: 7
Author(s): Sharmila Patel and Mark R. Player
Affiliation:
Keywords: CSF-1R, FMS, M-CSF, colony stimulating factor-1, anti-inflammatory, macrophages
Abstract: FMS is the exclusive receptor tyrosine kinase for colony-stimulating factor-1 (CSF-1, also known as M-CSF), which regulates the survival, proliferation, differentiation, and function of macrophage lineage cells. Since CSF-1 is overexpressed in many tumors and at sites of inflammation, small molecule inhibitors of CSF-1 appear to offer an attractive strategy for reducing macrophage numbers associated with cancer as well as autoimmune and inflammatory disease, such as rheumatoid arthritis (RA). Numerous FMS inhibitors with structurally distinct chemotypes have been developed and exhibit potent in vitro activity, but only a limited number of compounds have progressed clinically due to poor selectivity. To date, only a handful of FMS inhibitors have been tested in models of metastatic bone disease and RA. This review will summarize the biology of FMS and its function in bone physiology, inflammation, immunity, and cancer. In addition, efforts directed towards identifying FMS-selective small molecule inhibitors as well as the advancement of non-selective inhibitors in the clinic will be highlighted. Furthermore, emerging monoclonal antibody-based therapeutic strategies specifically targeting M-CSF will be described.
Export Options
About this article
Cite this article as:
Patel Sharmila and Player R. Mark, Colony-Stimulating Factor-1 Receptor Inhibitors for the Treatment of Cancer and Inflammatory Disease, Current Topics in Medicinal Chemistry 2009; 9 (7) . https://dx.doi.org/10.2174/156802609789007327
DOI https://dx.doi.org/10.2174/156802609789007327 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
Role of Renin-Angiotensin System in Inflammation, Immunity and Aging
Current Pharmaceutical Design A New Approach to the Inflammatory/Autoimmune Diseases
Recent Patents on Anti-Infective Drug Discovery Inflammation-Associated Changes in Bone Homeostasis
Inflammation & Allergy - Drug Targets (Discontinued) STAT3: A Molecular Target for Cancer Whose Time Has Come
Current Signal Transduction Therapy Editorial [Hot Topic: Recent Advances and Future Prospect in Protease Targeting (Executive Editor: B. Turk) ]
Current Pharmaceutical Design Atherosclerotic Plaque Stabilization - Potential Role for Immunomodulatory Therapy
Vascular Disease Prevention (Discontinued) Ustekinumab-induced Sarcoidosis in a Patient with Psoriatic Arthritis
Current Drug Safety New Au (III), Pt (II) and Pd (II) Complexes with Pentapeptide Glycylglycyl-L-Methyonyl-Glycyl-Glycine and Their Interaction with Calf Thymus DNA
Protein & Peptide Letters Complement and Microglia in the Neuropathogenesis of HIV Infection: Pro- and Anti-Inflammatory Aspects
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Aptamers Against Cell Surface Receptors: Selection, Modification and Application
Current Medicinal Chemistry Heparanase as a Target in Cancer Therapy
Current Cancer Drug Targets Myeloperoxidase: The Good, the Bad, and the Ugly
Current Immunology Reviews (Discontinued) Emerging Cytokines in Allergic Airway Inflammation: A Genetic Update
Current Immunology Reviews (Discontinued) The Potential of Microalgae for the Production of Bioactive Molecules of Pharmaceutical Interest
Current Pharmaceutical Biotechnology Pentraxins and Atherosclerosis: The Role of PTX3
Current Pharmaceutical Design Pharmacophore-Based 3DQSAR and Molecular Docking Studies to Identify New Non-Peptidic Inhibitors of Cathepsin S
Current Medicinal Chemistry Editorial [ UCTD and Unfinished Business ]
Current Rheumatology Reviews Randomized, Placebo Controlled Study of the Effects of Etoricoxib on Markers of Inflammation, Pain and Muscle Force After Eccentric Exercise
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued) Current Antioxidant Molecular Therapies for Oxidative Stress-Related Ailments
Current Gene Therapy The Function of the Selective Inhibitors of Cycloxygenase 2
Mini-Reviews in Medicinal Chemistry