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Pharmacological profile of AS1670542, a novel orally-active human thrombopoietin receptor agonist
- Source :
-
European Journal of Pharmacology . Jan2011, Vol. 650 Issue 1, p58-63. 6p. - Publication Year :
- 2011
-
Abstract
- Abstract: Eltrombopag, an orally-active small molecule thrombopoietin (TPO) receptor agonist, was used for the first time in 2008 to treat patients with chronic idiopathic thrombocytopenic purpura. Here, we investigated the pharmacological effect of a new orally-active small molecule TPO receptor agonist which may be effective in treating these patients. 50% effective concentration values for cell proliferation with AS1670542 or eltrombopag were 1.9 and 13nM, respectively, while those for megakaryocyte colony formation from human cord blood CD34+ cells with AS1670542 or eltrombopag were 260 and 950nM, respectively. On Day 14 after the start of administration, AS1670542 significantly increased the number of human platelets in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice with transplanted human hematopoietic stem cells at 0.3 (P <0.05); in contrast, while administration of eltrombopag also increased the numbers of these platelets at 30mg/kg/day (P =0.058), no statistical significance was noted in the increase. Here, we identified AS1670542, a novel orally-active TPO receptor agonist which mimics the biological activity of TPO and may demonstrate greater in vitro and in vivo pharmacologically efficacy than eltrombopag. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 650
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 55642357
- Full Text :
- https://doi.org/10.1016/j.ejphar.2010.09.072