Fingolimod  (Synonyms: FTY720 free base)

Fingolimod (FTY720 free base) is a brain-penetrant sphingosine 1-phosphate (S1P) antagonist with an IC₅₀ of 0.033 nM in K562 and NK cells. Fingolimod also is a pak1 activator, a immunosuppressant^{[1][2][3][4][5]}.

The monocyte-derived immature dendritic cells (iDCs) are pretreated with various concentrations of S1P for various periods of time prior to their incubation with NK cells. Four hours incubation of autologous or allogeneic iDCs with 0.2-20 μM of S1P significantly protectes these cells from NK cell lysis. The IC₅₀ values of S1P are calculated at 160 nM for autologous iDCs, and 34 nM for allogeneic iDCs. Next, the inhibitory effect of S1P is revered by various concentrations of Fingolimod or SEW2871, with an IC₅₀ effect of 173 or 15 nM, respectively^[1]. Fingolimod has been reported to reduce LPA synthesis via inhibition of the lysophospholipase autotaxin. Fingolimod treatment correlates with a significant elevation of axonal cAMP, a crucial factor for axonal outgrowth. Additionally, Fingolimod significantly reduces LPA levels in the injured nerve. PF-8380 treatment correlates with improved myelin thickness^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Fingolimod treatment results in significantly increased nerve conduction at 14 days post-crush in wildtype C57BL/6 mice. However, Foxn1^-/- mice, which are devoid of T- but not B-lymphocytes, show an improvement of nerve regeneration under fingolimod treatment. Although the mean increase in nerve conduction velocity in both fingolimod-treated and controlFoxn1^-/- mice implies a potentially positive role of T-lymphocyte deficiency on nerve regeneration, only fingolimod-treated Foxn1^-/- mice show a significant improvement compared to C57BL/6 controls and performed better in the functional analysis^[2]. Treatment of the animals with Fingolimod for 28 d results in a clear reduction in the binding of ¹⁸F-GE180 when compare with vehicle-treated animals and evaluated by ex vivo autoradiography. Quantification of the binding of the radiotracer revealed a significant reduction in the binding potential of ¹⁸F-GE180 (P<0.0001) after treatment with Fingolimod^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

307.47

C₁₉H₃₃NO₂

162359-55-9

Solid

White to off-white

OCC(CCC1=CC=C(CCCCCCCC)C=C1)(N)CO

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Rolin J, et al. FTY720 and SEW2871 reverse the inhibitory effect of S1P on natural killer cell mediated lysis of K562 tumor cells and dendritic cells but not on cytokine release. Cancer Immunol Immunother. 2010, 59(4), 575-586.  [Content Brief]

  [2]. Szepanowski F, et al. Fingolimod promotes peripheral nerve regeneration via modulation of lysophospholipid signaling. J Neuroinflammation. 2016 Jun 10;13(1):143.  [Content Brief]

  [3]. Airas L, et al. In vivo PET imaging demonstrates diminished microglial activation after fingolimod treatment in an animal model of multiple sclerosis. J Nucl Med. 2015 Feb;56(2):305-10.  [Content Brief]

  [4]. Shirakabe K, et al. Modification of lymphocyte migration to Peyer's patches by inhibition of sphingosine-1-phosphate lyase ameliorates murine colitis. J Gastroenterol Hepatol. 2018 Jan 15.  [Content Brief]

  [5]. Hunter S F, et al. The direct effects of fingolimod in the central nervous system: implications for relapsing multiple sclerosis[J]. CNS drugs, 2016, 30(2): 135-147.