Document Detail

Non-Cyclam Tetraamines inhibit CXC Chemokine Receptor Type 4 and target Glioma-Initiating Cells.
MedLine Citation:
PMID:  22909088     Owner:  NLM     Status:  Publisher    
The three stereoisomers of the non-cyclam compound 1 (1(R,R), 1(S,S), and the meso form 1(S,R)) and their corresponding tetrahydrochlorides were prepared from (S) and (R) 2-methylpiperidine. We have evaluated their inhibitory activity on the CXC Chemokine Receptor Type 4 (CXCR4), toxicity properties, and assessment of their effect on glioma initiating cells (GICs) in comparison with the prototype compound AMD3100. The IC50 values determined on human recombinant (CHO) cells showed very similar inhibitory activities albeit a lower KB for AMD3100, with the 1(R,R) isomer being second in potency. All the compounds showed low cardiac toxicity but, contrary to AMD3100, gave maximum nonlethal doses of around 2.0 mg/kg. The CXCR4 inhibitors had an effect on the state of differentiation of GICs decreasing the percentage of CD44+ cells in glioblastoma multiform neurospheres in vitro. Moreover, these CXCR4 inhibitors blocked the capacity of cells to initiate orthotopic tumors in immunocompromised mice.
Laia Ros-Blanco; Judit Anido; Ramon Bosser; Jose Este; Bonaventura Clotet; Ana Kosoy; Luis Ruiz-Avila; Jordi Teixido; Joan Seoane; Jose Ignacio Borrell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-21
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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