Fingolimod

Budde K, Schutz M, Glander P, Peters H, et al. 2006. FTY720 (fingolimod) in renal transplantation. Clin Transplant. 20 17-24. 

Kappos L, Antel J, Comi G, Montalban X, et al. 2006. Oral fingolimod (FYT720) for relapsing multiple sclerosis. NEJM. 355 1124-1140. 

Westhoff TH, Schmidt S, Glander P, Liefeld L, et al. 2007. The impact of FTY720 (fingolimod) on vasodilatory function and arterial elasticity in renal transplant patients. Nephrol Dial Transplant. 22 2354-2358. 

Sphingosine-1-phosphate receptor modulators FTY720 (Fingolimod)... 

Doi Y, Takeuchi H, Horiuchi H, Hanyu T, Kawanokuchi J, Jin S et al (2013) Fingolimod phosphate attenuates oligomeric amyloid P-induced neurotoxicity via increased brain-derived neurotrophic factor expression in neurons. PLoS One 8 e61988. doi 10.1371/ journal.pone.0061988... 

Nagaoka Y, Otsuki K, Fujita T et al (2008) Effects of phosphorylation of immunomodulatory agent FTY720 (fingolimod) on antiproliferative activity against breast and colon cancer cells. Biol Pharm Bull 31 1177-1181... 

The enantioselective synthesis of chiral isosteric phosphonate analogues of (2-amino-[2-(4- -octylphenyl)ethyl]-1,3-propanediol, Fingolimod (560) has been described by Bittman and co-workers. One of these analogues [( )-vinylphosphonate (5)], elicited a potent antiapoptotic effect in intestinal epithelial cells, suggesting that it exerted its action via the enantiose-lective activation of a receptor sphingosine 1-phosphate (SlPl). 

Fingolimod hydrochloride, the design of which was based on the fungal secondary metabolite myriocin, is a potent immunosuppressant that was approved as a new... 

Scheme 39 Use of the Sonogashira reactirai for the synthesis of the immunosuppressant Fingolimod hydrochloride...

Fingolimod (Gilenya) The First Oral Treatment for Multiple Sclerosis... 

Figure 1. Identification of ISP-las a potent immunosuppressant led to SAR efforts to identify fingolimod, the first oral treatment for multiple sclerosis.

Figure 3. Similar to sphingosine, fingolimod is a prodrug for an active phosphorylated metabolite.

Figure 4. Human metabolic profile generated using radiolabeled fingolimod.

Initial safety and efficacy of fingolimod was probed in two multicenter phase III trials targeting RRMS patients. In a one year study termed the Trial Assessing Injectable Interferon versus 0.5 mg FTY720 Oral in RRMS (TRANSFORMS) the 0.5 mg daily oral dose of fingolimod showed better efficacy than the first-line treatment Ilh betala (Ifh Bla) dosed intramuscular on endpoints that include annual relapse rate (ARR) and MRI assessments of brain volume loss, T1 lesion count (a measure of axonal death), and new T2 lesion count (a measure of axon demyelination) after one year. The trial was extended for one year (TRANSFORMS II) and patients administered the Ifh Bla were... 

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