Abstract
Pluripotent stem cells of the bone marrow are stimulated by different cytokines to proliferation and differentiation into various types of blood cells. These cytokines are mostly glycoproteins. Erythropoietin stimulates stem cells to the formation of erythrocytes while colony-stimulating factors cause the formation of different types of white blood cells. Stem cell factors play an important role in the maintenance and survival of blood cells of all types. Thrombopoietin stimulates stem cells to proliferation and formation of blood platelets. Granulocyte colony-stimulating factor is probably the most important drug in use. It stimulates stem cells to the formation of neutrophile granulocytes. It is often used in recombinant forms such as filgrastim in the treatment of neutropenia in cancer chemotherapy or AIDS. Its pegylated conjugates such as pegfilgrastim are also available. Its activity can be supported by plerixafor, a small molecule – bicyclam derivative acting as an indirect agonist of stem cells factor. It acts as an antagonist of CXCR4 receptor activation of which brakes hematopoiesis. The treatment of conditions accompanied by thrombocytopenia such as idiopathic thrombocytopenic purpura is currently not performed by thrombopoietin but synthetic agonists of its receptor are preferred. Romiplostim is a peptibody. It consists of a protein part interacting with the thrombopoietin receptor which is, however, different from thrombopoietin, and of Fc fragment of immunoglobulin G1. In contrast, small molecule thrombopoietin receptor agonists represented by eltrombopag can be given orally unlike all of the above.
Keywords: Colony-stimulating factors, stem-cell factors, pegylation, plerixafor, thrombopoietin, romiplostim, eltrombopag.
Mini-Reviews in Medicinal Chemistry
Title:Protein and Small-Molecule Leucopoiesis and Thrombopoiesis Stimulators
Volume: 21 Issue: 13
Author(s): Oldřich Farsa*Peter Zubáč
Affiliation:
- Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Brno,Czech Republic
Keywords: Colony-stimulating factors, stem-cell factors, pegylation, plerixafor, thrombopoietin, romiplostim, eltrombopag.
Abstract: Pluripotent stem cells of the bone marrow are stimulated by different cytokines to proliferation and differentiation into various types of blood cells. These cytokines are mostly glycoproteins. Erythropoietin stimulates stem cells to the formation of erythrocytes while colony-stimulating factors cause the formation of different types of white blood cells. Stem cell factors play an important role in the maintenance and survival of blood cells of all types. Thrombopoietin stimulates stem cells to proliferation and formation of blood platelets. Granulocyte colony-stimulating factor is probably the most important drug in use. It stimulates stem cells to the formation of neutrophile granulocytes. It is often used in recombinant forms such as filgrastim in the treatment of neutropenia in cancer chemotherapy or AIDS. Its pegylated conjugates such as pegfilgrastim are also available. Its activity can be supported by plerixafor, a small molecule – bicyclam derivative acting as an indirect agonist of stem cells factor. It acts as an antagonist of CXCR4 receptor activation of which brakes hematopoiesis. The treatment of conditions accompanied by thrombocytopenia such as idiopathic thrombocytopenic purpura is currently not performed by thrombopoietin but synthetic agonists of its receptor are preferred. Romiplostim is a peptibody. It consists of a protein part interacting with the thrombopoietin receptor which is, however, different from thrombopoietin, and of Fc fragment of immunoglobulin G1. In contrast, small molecule thrombopoietin receptor agonists represented by eltrombopag can be given orally unlike all of the above.
Export Options
About this article
Cite this article as:
Farsa Oldřich *, Zubáč Peter , Protein and Small-Molecule Leucopoiesis and Thrombopoiesis Stimulators, Mini-Reviews in Medicinal Chemistry 2021; 21 (13) . https://dx.doi.org/10.2174/1389557521999201230195926
DOI https://dx.doi.org/10.2174/1389557521999201230195926 |
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
-
Drug Targeting Based on a New Concept-Targeting Against TLR4 as an Example
Endocrine, Metabolic & Immune Disorders - Drug Targets Peptide-based Vaccines in the Treatment of Specific Allergy
Current Drug Targets - Inflammation & Allergy Mechanism of Action of Flavonoids in Prevention of Inflammation- Associated Skin Cancer
Current Medicinal Chemistry Mechanisms of Neurodegeration in Type 2 Diabetes and the Neuroprotective Potential of Dipeptidyl Peptidase 4 Inhibitors
Current Medicinal Chemistry Use of Recombinant Human Erythropoietin as an Antianemic and Performance Enhancing Drug
Current Pharmaceutical Biotechnology Urinary Tract Infection in Children
Recent Patents on Inflammation & Allergy Drug Discovery Bone Seeking Radiopharmaceuticals for Palliation of Pain in Cancer Patients with Osseous Metastases
Anti-Cancer Agents in Medicinal Chemistry Regulation of βAPP and PrPc Cleavage by α-Secretase: Mechanistic and Therapeutic Perspectives
Current Alzheimer Research Chemical Modifications and Biological Activities of Polysaccharides
Current Drug Targets Cross-Talk between Oxidative Stress and Pro-Inflammatory Cytokines in Acute Pancreatitis: A Key Role for Protein Phosphatases
Current Pharmaceutical Design Alteration of Isocitrate Dehydrogenase Following Acute Ischemic Injury as a Means to Improve Cellular Energetic Status in Neuroadaptation
CNS & Neurological Disorders - Drug Targets Nutrigenomic Analysis of Diet-Gene Interactions on Functional Supplements for Weight Management
Current Genomics Mitochondria Sentencing About Cellular Life and Death: A Matter of Oxidative Stress
Current Pharmaceutical Design Nonalcoholic Fatty Liver Disease: The Pathogenetic Roles of Insulin Resistance and Adipocytokines
Current Molecular Medicine Novel Drug Therapies for Fertility Preservation in Men Undergoing Chemotherapy: Clinical Relevance of Protector Agents
Current Medicinal Chemistry Exploring the Anti-Neuroinflammatory Potential of Steroid and Terpenoid-Derived Phytochemicals to Combat Alzheimer's Disease
Current Pharmaceutical Design Pathological Role for Exocytotic Glutamate Release from Astrocytes in Hepatic Encephalopathy
Current Neuropharmacology Phage Display Selection and Evaluation of Cancer Drug Targets
Current Cancer Drug Targets Treatment with Paracetamol is not Associated with Increased Airway Sensitivity and Risk of Asthma in Rats
Current Drug Safety Toxicity of Nanoparticles
Current Medicinal Chemistry