Document Detail


Orally bioavailable isothioureas block function of the chemokine receptor CXCR4 in vitro and in vivo.
MedLine Citation:
PMID:  19053768     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The interaction of the chemokine receptor CXCR4 with its ligand CXCL12 is involved in many biological processes such as hematopoesis, migration of immune cells, as well as in cancer metastasis. CXCR4 also mediates the infection of T-cells with X4-tropic HIV functioning as a coreceptor for the viral envelope protein gp120. Here, we describe highly potent, selective CXCR4 inhibitors that block CXCR4/CXCL12 interactions in vitro and in vivo as well as the infection of target cells by X4-tropic HIV.
Authors:
Gebhard Thoma; Markus B Streiff; Jiri Kovarik; Fraser Glickman; Trixie Wagner; Christian Beerli; Hans-Günter Zerwes
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  51     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-18     Completed Date:  2009-01-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7915-20     Citation Subset:  IM    
Affiliation:
Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4002 Basel, Switzerland. gebhard.thoma@novartis.com
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Biological Availability
Chemistry, Pharmaceutical / methods
Chemokine CXCL12 / chemistry
Chemokines / metabolism
Drug Design
HIV Envelope Protein gp120 / chemistry
Humans
Inhibitory Concentration 50
Models, Chemical
Rats
Receptors, CXCR4 / antagonists & inhibitors,  chemistry*
T-Lymphocytes / metabolism,  virology
Thiourea / chemistry*
Chemical
Reg. No./Substance:
0/CXCL12 protein, human; 0/CXCR4 protein, human; 0/Chemokine CXCL12; 0/Chemokines; 0/HIV Envelope Protein gp120; 0/Receptors, CXCR4; 62-56-6/Thiourea

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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