| Biologic aspects of thrombopoietin and the development of novel thrombopoietic agents for clinical use. | |
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MedLine Citation:
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PMID: 17985999 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thrombocytopenia is a frequent finding in several clinical settings, including bone marrow failure associated with various disorders, immune-mediated thrombocytopenia, and chronic liver diseases. Currently, there is an unmet need for thrombopoietic agents to treat this condition. Thrombopoietin (TPO) is the key cytokine involved in thrombopoiesis, and is the endogenous ligand for the thrombopoietin receptor that is expressed on the surface of megakaryocytes and megakaryocytic precursors. Although clinical trials with first generation thrombopoietic agents were abruptly discontinued after the development of TPO autoantibodies had been observed, non-antigenic second generation thrombopoietic growth factors with unique pharmacological properties have been developed. These include TPO peptide mimetics (AMG 531 and Fab59), TPO non-peptide mimetics (eltrombopag, NIP-004, and AKR-501) and TPO agonist antibodies. All of these bind to and activate the TPO receptor in different ways but all via JAK2/STAT signalling pathways, producing a dose-dependent rise in platelet counts. In view of their use as therapeutic agents, nonpeptide agonists seem to have an advantage over peptide agonists, in that they could be orally bioavailable. The aim of the present review is to illustrate the biology of TPO and its receptor, and to describe the structure and function of the new thrombopoietic agents. |
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Authors:
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Maria Laura Evangelista; Sergio Amadori; Roberto Stasi |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Current drug discovery technologies Volume: 4 ISSN: 1570-1638 ISO Abbreviation: Curr Drug Discov Technol Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-11-07 Completed Date: 2008-01-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101157212 Medline TA: Curr Drug Discov Technol Country: United Arab Emirates |
Other Details:
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Languages: eng Pagination: 162-73 Citation Subset: IM |
Affiliation:
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Department of Medical Sciences, Regina Apostolorum Hospital, Via S. Francesco 50, 00041 Albano Laziale, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Humans Models, Biological Molecular Sequence Data Molecular Structure Receptors, Thrombopoietin / agonists* Thrombocytopenia / drug therapy Thrombopoietin / chemistry, pharmacology*, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Thrombopoietin; 9014-42-0/Thrombopoietin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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