Fingolimod hydrochloride

Description

Approved by the U.S. FDA in September 2010, fingolimod (also referred to as FTY720) is the first approved oral therapy for the relapsing-remitting form ofmultiple sclerosis (RRMS). Because of fingolimod’s structural resemblance to sphingosine, a metabolite of sphingolipids that constitutes the cell membrane of all eukaryotic cells, it was hypothesized that fingolimod may be affecting sphingolipid metabolism in cells. A series of elegant in vitro and in vivo studies confirmed that fingolimod is converted to (S)-fingolimod phosphate primarily by sphingosine kinase- 2 and that (S)-fingolimod phosphate mediates multiple biological processes by binding to novel GPCR’s referred to as sphingosine-1-phosphate (S1P) receptors. S1P receptors are divided into five subtypes, S1P_1–5, which have varying tissue and cellular distribution. S1P_1–3 receptors are ubiquitously expressed in the immune, cardiovascular, and central nervous systems, S1P4 is restricted to the hematopoietic system, and S1P₅ is mostly localized in the white matter of CNS. S1P_1–3 receptors play important roles in endothelial barrier function, maintaining vascular tone, regulating heart rate and allowing for lymphocyte egress fromsecondary lymphoid organs. The functional role of S1P₄ is unknown,while the S1P5 receptor is thought to be involved in natural killer cell trafficking and oligodendrocyte function.

The Uses of Fingolimod hydrochloride

Fingolimod Hydrochloride is a derivative of ISP-1 (myriocin), a fungal metabolite of the Chinese herb Iscaria sinclarii as well as a structural analogue of Sphingosine. Fingolimod is a novel immune modulator that prolongs allograft transplant survival in numerous models by inhibiting lymphocyte emigration from lymphoid organs. Fingolimod is reported to be phosphorylated by sphingosine kinase to FTY720-P, which has been shown to potently stimulate GTPgS binding activity in S1P-transfected CHO cells (EC50 = 210 pM, 4.9 nM, 4.3 nM, and 1 nM for S1P1, S1P3, S1P4 and S1P5, respectively).

What are the applications of Application

FTY720 is a cell-permeable immunosuppressive agent