Title:Molecular Targets of FTY720 (Fingolimod)
Volume: 12
Issue: 10
Author(s): M.R. Pitman, J.M. Woodcock, A.F. Lopez and S.M. Pitson
Affiliation:
Keywords:
Apoptosis, cancer, FTY720, fingolimod, lymphopenia, lysophospholipid, sphingosine, sphingosine 1-phosphate, therapeutic drug, Gilenya™, myriocin, immunosuppressive activity, immuno-suppressants, toxicity, multiple sclerosis
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.
