fty720

Fingolimod hydrochloride (FTY720) , a novel immune modulator, is a sphingosine 1-phosphate (S1P) antagonist (IC50: 0.033 nM in K562 and NK cells).

Fingolimod (FTY-720A) is an antagonist of sphingosine 1-phosphate (S1P) (IC50 of 0.033 nM in K562 and NK cells).

FTY720 (S)-Phosphate is the active stereoisomeric phosphate derivative of FTY720 that acts as a potent modulator of sphingosine-1-phosphate (S1P) receptors. FTY720 (S)-Phosphate binds to S1P receptor subtypes S1P1, S1P3, S1P4, and S1P5 with Ki values of 2.1, 5.9, 23, and 2.2 nM respectively, causing receptor internalization on lymphocytes， preventing S1P-mediated lymphocyte egress from lymphoid tissues. FTY720 (S)-Phosphate also enhances endothelial barrier integrity, stimulates transporters such as Abcb1 and Abcc1, and inhibits cytosolic phospholipase A2 activity, highlighting its multifunctional pharmacological properties, making it an compound of interest in the research of diseases including multiple sclerosis, autoimmune diseases and cancer.

Azido-FTY720 (azido-Fingolimod) is an analogue of FTY720 featuring an azido group suitable for click chemistry reactions. FTY720 is an orally available S1P analogue and S1P1R modulator capable of crossing the blood-brain barrier (BBB), reducing neuroinflammation, and is indicated for multiple sclerosis (MS).

FTY720-C2 is an FTY720 analog. It acts as an effective stimulator of the activity of the protein phosphatase 2A.

(R)-FTY720-OMe is a structural analogue of FTY720 which acts as a specific competitive inhibitor of sphingosine kinase 2 (SK2). Furthermore, (R)-FTY720-OMe does not inhibit sphingosine kinase 1 (SK1) activity.

FTY720 (S)-Phosphate, an S1P receptor 1 (S1PR1) agonist, is utilized in studying acute inflammatory diseases, including acute lung injury.

FTY720, an immune modulator, down-regulates sphingosine-1-phosphate (S1P) receptors, enhances the activity of sphingosine transporter Abcb1 and leukotriene C4 transporter Abcc1, and inhibits cytosolic phospholipase A2 activity. Its efficacy relies on in vivo phosphorylation by sphingosine kinases, resulting in FTY720-phosphate which also down-regulates S1P receptors. NBD-FTY720, a fluorescently-labeled analog of FTY720, retains the hydroxy methyl side chain targeted for phosphorylation, suggesting potential phosphorylation in vivo.

MP07-66 is a novel FTY720-analog devoid of immunosuppressive effects leads to the reactivation of PP2A, which in turn triggers apoptosis of CLL cells.

(R)-FTY-720 Vinylphosphonate is a sphingosine 1-phosphate type 1 (S1P1) receptor agonist and lacks anti-apoptotic activity.

(S)-FTY-720 Vinylphosphonate inhibits sphingosine kinase 1 and promotes its proteasomal degradation in human pulmonary artery smooth muscle, breast cancer cells, and androgen-independent prostate cancer cells.

BMS-986104 is an effective selective modulator of the S1P1 receptor. It demonstrates efficacy in the mouse EAE model, comparable to that of FTY720. Furthermore, BMS-986104 shows promising remyelination properties in three-dimensional brain cell cultures subjected to lysophosphatidylcholine (LPC)-induced demyelination.

AAL-149, an analog of FTY720 and a TRPM7 inhibitor (IC50 = 1.081 μM), exhibits multiple anti-inflammatory effects without targeting S1P receptors. It is applicable in anti-inflammatory research.

pro-FTY is an anticancer prodrug of FTY720 and acts as a sphingosine-1-phosphate (S1P) inhibitor. It specifically inhibits S1P signaling in cancer cells via a drug delivery system (DDS) that reacts with acrolein. pro-FTY significantly reduces the survival of breast cancer cells, including multidrug-resistant cells and organoids resistant to Paclitaxel or Doxorubicin. Additionally, pro-FTY effectively suppresses tumor growth in xenograft mouse models of 4T1 cells or organoids while avoiding lymphopenia.

ST1060 is a derivative of FTY720 and serves as a selective inhibitor of ceramide synthase 2 (CerS2). It effectively reduces the levels of long-chain dihydroceramides (dhCer) catalyzed by CerS2, with IC50 values for C24:0 and C24:1 being 63.6 μM and 61.3 μM, respectively. ST1060 is applicable in the research of ceramide metabolism disorders.