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Molecular Targets of FTY720 (Fingolimod)

[ Vol. 12 , Issue. 10 ]

Author(s):

M.R. Pitman, J.M. Woodcock, A.F. Lopez and S.M. Pitson   Pages 1207 - 1219 ( 13 )

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, cancer, FTY720, fingolimod, lymphopenia, lysophospholipid, sphingosine, sphingosine 1-phosphate, therapeutic drug, Gilenya™, myriocin, immunosuppressive activity, immuno-suppressants, toxicity, multiple sclerosis

Affiliation:

Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide SA 5000, Australia.



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