フィンゴリモド塩酸塩

外観

白色～ほとんど白色、結晶～粉末又は塊

溶解性

水、メタノール及びエタノール(99.5)に溶けやすく、アセトニトリルにほとんど溶けない。

用途

スフィンゴシンのアナログで す。体内でりん酸化され、スフィンゴシン 1- りん酸 1 受容体のアゴニストとして働きま す。自己反応性リンパ球の中枢神経系への浸 潤を妨げ、免疫抑制作用を示します。

効能

免疫抑制薬, スフィンゴシン一リン酸受容体作動薬

商品名

イムセラ (田辺三菱製薬); ジレニア (ノバルティスファーマ)

説明

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.

化学的特性

White Solid

使用

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).

定義

ChEBI: The hydrochloride salt of 2-amino-2-[2-(4-octylphenyl) ethyl]-1,3-propanediol (fingolimod).

臨床応用

Fingolimod hydrochloride is an immunosuppressive drug developed by Novartis and approved in the U.S., Europe, and Australia in 2010 for the treatment of multiple sclerosis. The structure of fingolimod derives from the naturally-occurring myriocin (ISP-1) metabolite of the fungus I. sinclairii and the aminoalcohol functionality within the drug possesses structural similarity to the sphingosine family of natural products.