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Type: Journal article
Title: Molecular targets of FTY720 (Fingolimod)
Author: Pitman, M.
Woodcock, J.
Lopez, A.
Pitson, S.
Citation: Current Molecular Medicine, 2012; 12(10):1207-1219
Publisher: Bentham Science
Issue Date: 2012
ISSN: 1566-5240
Statement of
M.R. Pitman, J.M. Woodcock, A.F. Lopez and S.M. Pitson
Abstract: 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 nonphosphorylated 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.
Keywords: Apoptosis
sphingosine 1-phosphate
therapeutic drug, Gilenya™
immunosuppressive activity
multiple sclerosis
Rights: Copyright status unknown
DOI: 10.2174/156652412803833599
Grant ID:
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