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