Cell lines

MCF-7, MDA-MB-231, Sk-Br-3, HCT-116 and SW620 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Reaction Conditions

IC50: 79.1 μM (MCF-7), 59.9 μM (MDA-MB-231), 72.9 μM (Sk-Br-3), > 100 μM (HCT-116) and 40.0 μM (SW620); 48 hours

Applications

The IC50 values of fingolimod were determined by a WST-1 assay. The results demonstrated that treatment of the compound caused cell death in a dose-dependent manner. Fingolimod exhibited comparatively low IC50 values within the concentration range of 5-7μM for all of the cells tested in this study.

Animal models

C57BL/6J mice

Dosage form

Intraperitoneal injection, 0.1 mg per kg of body weight

Applications

As early as 30 min after injection of fingolimod (0.1 mg per kg of body weight), the levels of phosphorylated ERK1/2 (pERK1/2) were significantly increased in hippocampal neurons. After an additional 30 min, BDNF mRNA levels were elevated, and protein levels were significantly increased in the hippocampus, the cortex, and the striatum after 48 h.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

• Int J Mol Med 48.5 (2021): 1-13. PMID:34549307

Fingolimod is a mechanistically novel, orally bioavailable therapy for multiple sclerosis (MS) [1].

Fingolimod is a FDA approved drug for Multiple sclerosis treatment. It is a folk medicine emerged from Fungi. Fingolimod was firstly found to be a therapeutic agent in organ transplantation. Then Fingolimod was found to have similar structure with natural sphingosine and interact with S1P1, S1P4, S1P5 and S1P3 receptors as high affinity agonist with EC50 values of 0.3-3.1 nM. It plays the role in MS treatment through receptor-mediated actions both on the immune system and in the CNS. Fingolimod can prevent normal lymphocyte egress and reduce the infiltration of autoaggressive lymphocytes into the CNS [1, 2].

References:
[1] Chun J, Brinkmann V. A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya). Discovery medicine, 2011, 12(64): 213.
[2] Chun J, Hartung H P. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clinical neuropharmacology, 2010, 33(2): 91.