| Pharmacological profile of AS1670542, a novel orally-active human thrombopoietin receptor agonist. | |
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MedLine Citation:
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PMID: 20950606 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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Masaki Abe; Ken-Ichi Suzuki; Chinatsu Sakata; Keizo Sugasawa; Fukushi Hirayama; Yuji Koga; Tomihisa Kawasaki; Shin Naganuma; Hiroyuki Itoh |
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Publication Detail:
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Type: Journal Article Date: 2010-10-13 |
Journal Detail:
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Title: European journal of pharmacology Volume: 650 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 58-63 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. masaki.abe@jp.astellas.com |
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