Mechanisms and therapeutic prospects of thrombopoietin receptor agonists

James Bussel, Austin Kulasekararaj, Nichola Cooper, Amit Verma, Ulrich Steidl, John W. Semple, Britta Will

Research output: Contribution to journalReview article

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, 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.

Original languageEnglish (US)
Pages (from-to)262-278
Number of pages17
JournalSeminars in Hematology
Volume56
Issue number4
DOIs
StatePublished - Oct 2019

Fingerprint

Thrombopoietin Receptors
Aplastic Anemia
Immunosuppressive Agents
Therapeutics
Idiopathic Thrombocytopenic Purpura
Myelodysplastic Syndromes
Thrombocytopenia
Drug Therapy
Pharmaceutical Preparations

Keywords

  • Eltrombopag
  • Mechanism of action
  • Megakaryopoiesis
  • Romiplostim
  • Thrombocytopenia

ASJC Scopus subject areas

  • Hematology

Cite this

Mechanisms and therapeutic prospects of thrombopoietin receptor agonists. / Bussel, James; Kulasekararaj, Austin; Cooper, Nichola; Verma, Amit; Steidl, Ulrich; Semple, John W.; Will, Britta.

In: Seminars in Hematology, Vol. 56, No. 4, 10.2019, p. 262-278.

Research output: Contribution to journalReview article

Bussel, James ; Kulasekararaj, Austin ; Cooper, Nichola ; Verma, Amit ; Steidl, Ulrich ; Semple, John W. ; Will, Britta. / Mechanisms and therapeutic prospects of thrombopoietin receptor agonists. In: Seminars in Hematology. 2019 ; Vol. 56, No. 4. pp. 262-278.
@article{dde02099e83d471eb0a977da560c646a,
title = "Mechanisms and therapeutic prospects of thrombopoietin receptor agonists",
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, 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.",
keywords = "Eltrombopag, Mechanism of action, Megakaryopoiesis, Romiplostim, Thrombocytopenia",
author = "James Bussel and Austin Kulasekararaj and Nichola Cooper and Amit Verma and Ulrich Steidl and Semple, {John W.} and Britta Will",
year = "2019",
month = "10",
doi = "10.1053/j.seminhematol.2019.09.001",
language = "English (US)",
volume = "56",
pages = "262--278",
journal = "Seminars in Hematology",
issn = "0037-1963",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Mechanisms and therapeutic prospects of thrombopoietin receptor agonists

AU - Bussel, James

AU - Kulasekararaj, Austin

AU - Cooper, Nichola

AU - Verma, Amit

AU - Steidl, Ulrich

AU - Semple, John W.

AU - Will, Britta

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - Eltrombopag

KW - Mechanism of action

KW - Megakaryopoiesis

KW - Romiplostim

KW - Thrombocytopenia

UR - http://www.scopus.com/inward/record.url?scp=85075365592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075365592&partnerID=8YFLogxK

U2 - 10.1053/j.seminhematol.2019.09.001

DO - 10.1053/j.seminhematol.2019.09.001

M3 - Review article

AN - SCOPUS:85075365592

VL - 56

SP - 262

EP - 278

JO - Seminars in Hematology

JF - Seminars in Hematology

SN - 0037-1963

IS - 4

ER -