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Molecular targets of FTY720 (fingolimod).
MedLine Citation:
PMID:  22834825     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
FTY720 is a recently approved first line therapy for relapsing forms of multiple sclerosis. In this context, FTY720 is a pro-drug, with its anti-multiple sclerosis, immunosuppressive effects largely elicited following its phosphorylation by sphingosine kinase 2 and subsequent modulation of G protein-coupled sphingosine 1-phosphate (S1P) receptor 1 that induces lymphopenia by altering lymphocyte trafficking. A number of other biological effects of FTY720 have, however, been described, including considerable evidence that this drug also has anti-cancer properties. These other effects of FTY720 are independent of S1P receptors, and appear facilitated by modulation of a range of other recently described protein targets by non-phosphorylated FTY720. Here, we review the direct targets of FTY720 that contribute to its anti-cancer properties. We also discuss other recently described protein effectors that, in combination with S1P receptors, appear to contribute to its immunosuppressive effects.
Authors:
Melissa R Pitman; Joanna M Woodcock; Angel F Lopez; Stuart M Pitson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-23
Journal Detail:
Title:  Current molecular medicine     Volume:  -     ISSN:  1875-5666     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101093076     Medline TA:  Curr Mol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide SA 5000, Australia. stuart.pitson@health.sa.gov.au.
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