Mechanisms and therapeutic prospects of thrombopoietin receptor agonists
(2019) In Seminars in Hematology 56(4). p.262-278- Abstract
The second-generation thrombopoietin (TPO) receptor agonists eltrombopag and romiplostim are potent activators of megakaryopoiesis and represent a growing treatment option for patients with thrombocytopenic hematological disorders. Both TPO receptor agonists have been approved worldwide for the treatment of children and adults with chronic immune thrombocytopenia. In the EU and USA, eltrombopag is approved for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy and in the USA for the first-line treatment of severe aplastic anemia in combination with immunosuppressive therapy. Eltrombopag has also shown efficacy in several other disease settings, for example,... (More)
The second-generation thrombopoietin (TPO) receptor agonists eltrombopag and romiplostim are potent activators of megakaryopoiesis and represent a growing treatment option for patients with thrombocytopenic hematological disorders. Both TPO receptor agonists have been approved worldwide for the treatment of children and adults with chronic immune thrombocytopenia. In the EU and USA, eltrombopag is approved for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy and in the USA for the first-line treatment of severe aplastic anemia in combination with immunosuppressive therapy. Eltrombopag has also shown efficacy in several other disease settings, for example, chemotherapy-induced thrombocytopenia, selected inherited thrombocytopenias, and myelodysplastic syndromes. While both TPO receptor agonists stimulate TPO receptor signaling and enhance megakaryopoiesis, their vastly different biochemical structures bestow upon them markedly different molecular and functional properties. Here, we review and discuss results from preclinical and clinical studies on the functional and molecular mechanisms of action of this new class of drug.
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- author
- Bussel, James ; Kulasekararaj, Austin ; Cooper, Nichola ; Verma, Amit ; Steidl, Ulrich ; Semple, John W. LU and Will, Britta
- organization
- publishing date
- 2019-10-19
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Eltrombopag, Mechanism of action, Megakaryopoiesis, Romiplostim, Thrombocytopenia
- in
- Seminars in Hematology
- volume
- 56
- issue
- 4
- pages
- 262 - 278
- publisher
- Elsevier
- external identifiers
-
- pmid:31836033
- scopus:85075365592
- ISSN
- 0037-1963
- DOI
- 10.1053/j.seminhematol.2019.09.001
- language
- English
- LU publication?
- yes
- id
- 2e786ed9-f17a-4b9a-947b-78ad201791cf
- date added to LUP
- 2019-12-03 10:12:52
- date last changed
- 2024-07-10 06:55:22
@article{2e786ed9-f17a-4b9a-947b-78ad201791cf,
abstract = {{<p>The second-generation thrombopoietin (TPO) receptor agonists eltrombopag and romiplostim are potent activators of megakaryopoiesis and represent a growing treatment option for patients with thrombocytopenic hematological disorders. Both TPO receptor agonists have been approved worldwide for the treatment of children and adults with chronic immune thrombocytopenia. In the EU and USA, eltrombopag is approved for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy and in the USA for the first-line treatment of severe aplastic anemia in combination with immunosuppressive therapy. Eltrombopag has also shown efficacy in several other disease settings, for example, chemotherapy-induced thrombocytopenia, selected inherited thrombocytopenias, and myelodysplastic syndromes. While both TPO receptor agonists stimulate TPO receptor signaling and enhance megakaryopoiesis, their vastly different biochemical structures bestow upon them markedly different molecular and functional properties. Here, we review and discuss results from preclinical and clinical studies on the functional and molecular mechanisms of action of this new class of drug.</p>}},
author = {{Bussel, James and Kulasekararaj, Austin and Cooper, Nichola and Verma, Amit and Steidl, Ulrich and Semple, John W. and Will, Britta}},
issn = {{0037-1963}},
keywords = {{Eltrombopag; Mechanism of action; Megakaryopoiesis; Romiplostim; Thrombocytopenia}},
language = {{eng}},
month = {{10}},
number = {{4}},
pages = {{262--278}},
publisher = {{Elsevier}},
series = {{Seminars in Hematology}},
title = {{Mechanisms and therapeutic prospects of thrombopoietin receptor agonists}},
url = {{http://dx.doi.org/10.1053/j.seminhematol.2019.09.001}},
doi = {{10.1053/j.seminhematol.2019.09.001}},
volume = {{56}},
year = {{2019}},
}