Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
Blood, 1 June 2006, Vol. 107, No. 11, pp. 4300-4307.
Prepublished online as a Blood First Edition Paper on February 16, 2006; DOI 10.1182/blood-2005-11-4433.


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2005-11-4433v1
107/11/4300    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nakamura, T.
Right arrow Articles by Tsuruzoe, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakamura, T.
Right arrow Articles by Tsuruzoe, N.
Related Collections
Right arrow Hematopoiesis and Stem Cells
Right arrow Hemostasis, Thrombosis, and Vascular Biology
Right arrow Signal Transduction
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

HEMATOPOIESIS

A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis

Takanori Nakamura, Yoshitaka Miyakawa, Atsushi Miyamura, Akiko Yamane, Hidenori Suzuki, Mamoru Ito, Yasuyuki Ohnishi, Norihisa Ishiwata, Yasuo Ikeda, and Nobutomo Tsuruzoe

From the Pharmaceutical Research Department, Biological Research Laboratories, Nissan Chemical Industries, Saitama; Department of Internal Medicine, Keio University School of Medicine, Tokyo; Medical Research & Development Center, Tokyo Metropolitan Institute of Medical Science, Tokyo; and Central Institute for Experimental Animals, Kanagawa, Japan.

NIP-004 is a novel synthetic compound developed to display human thrombopoietin (TPO) receptor (c-Mpl) agonist activity. NIP-004 displays species specificity, stimulating proliferation or differentiation of human c-Mpl–expressing cells such as UT-7/TPO and human CD34+ cells but not murine c-Mpl–expressing cells or cynomolgus monkey cells. To test the mechanism of its action, we constructed mutant forms of c-Mpl; murine c-MplL490H dis-played a response to NIP-004, whereas human c-MplH499L lost this response, indicating that histidine in the transmembrane domain of c-Mpl is essential for its activity. Because histidine is not present in the c-Mpl transmembrane domain of rats, hamsters, rhesus macaques, and cynomolgus monkeys, we examined the in vivo efficacy of NIP-004 using mice that received xenotransplants. In immunodeficient nonobese diabetic (NOD)/Shi-scid, IL-2R{gamma}null (NOG) mice receiving transplants of umbilical cord blood–derived CD34+ cells, NIP-004 increased human megakaryoblasts, mature megakaryocytes, and circulating human platelets 6-fold, the latter being morphologically and functionally indistinguishable from normal human platelets. These observations indicate that NIP-004 is a novel human c-Mpl activator and induces human thrombopoiesis.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
haematolHome page
W. Nogami, H. Yoshida, K. Koizumi, H. Yamada, K. Abe, A. Arimura, N. Yamane, K. Takahashi, A. Yamane, A. Oda, et al.
The effect of a novel, small non-peptidyl molecule butyzamide on human thrombopoietin receptor and megakaryopoiesis
Haematologica, October 1, 2008; 93(10): 1495 - 1504.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. M. Jenkins, D. Williams, Y. Deng, J. Uhl, V. Kitchen, D. Collins, and C. L. Erickson-Miller
Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist
Blood, June 1, 2007; 109(11): 4739 - 4741.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
M.-J. Kim, S. H. Park, S. J. Opella, T. H. Marsilje, P.-Y. Michellys, H. M. Seidel, and S.-S. Tian
NMR Structural Studies of Interactions of a Small, Nonpeptidyl Tpo Mimic with the Thrombopoietin Receptor Extracellular Juxtamembrane and Transmembrane Domains
J. Biol. Chem., May 11, 2007; 282(19): 14253 - 14261.
[Abstract] [Full Text] [PDF]


Home page
ASH Education BookHome page
B. Andemariam, B. Psaila, and J. B. Bussel
Novel Thrombopoietic Agents
Hematology, January 1, 2007; 2007(1): 106 - 113.
[Abstract] [Full Text] [PDF]



 click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020