Abstract
FTY720 is an analog of sphingosine-1-phosphate (S1P) derived from the ascomycete Cordyceps sinensis. As a new immunosuppressant, FTY720 is widely used to treat multiple sclerosis. FTY720 binds to the S1P receptor after phosphorylation, thereby exerting immunosuppressive effects. The nonphosphorylated form of FTY720 can induce cell apoptosis, enhance chemotherapy sensitivity, and inhibit tumor metastasis of multiple tumors by inhibiting SPHK1 (sphingosine kinase 1) and activating PP2A (protein phosphatase 2A) and various cell death pathways. FTY720 can induce neutrophil extracellular traps to neutralize and kill pathogens in vitro, thus exerting anti- infective effects. At present, a series of FTY720 derivatives, which have pharmacological effects such as anti-tumor and alleviating airway hyperresponsiveness, have been developed through structural modification. This article reviews the pharmacological effects of FTY720 and its derivatives.
Graphical Abstract
[http://dx.doi.org/10.7164/antibiotics.47.208] [PMID: 8150717];
(b) Fujita, T, Inoue K, Yamamoto S, Ikumoto T, Sasaki S, Toyama R, Chiba K, Hoshino Y, Okumoto T. Fungal metabolites. part 11. A potent immunosuppressive activity found in isaria sinclairii metabolite. J. Antibiot., 1994, 47, 208-15.
[http://dx.doi.org/10.7164/antibiotics.47.208] [PMID: 8150717];
(c) Fujita, T, Hamamichi N, Kiuchi M, Matsuzaki T, Kitao Y, Inoue K, Hirose R, Yoneta M, Sasaki S, Chiba K. Determination of absolute configuration and biological activity of new immunosuppressants, mycestericins D, E, F and G. J. Antibiot., 1996, 49, 846-53. Erratum in: J Antibiot (Tokyo) 1996 Dec;49(12):C-3
[http://dx.doi.org/10.7164/antibiotics.49.846.] [PMID: 8931716]
[http://dx.doi.org/10.1074/jbc.C200176200] [PMID: 11967257]
[http://dx.doi.org/10.3892/or.2021.8251] [PMID: 34958115]
[http://dx.doi.org/10.3390/ijms22147259] [PMID: 34298877]
[http://dx.doi.org/10.3389/fcimb.2021.627917] [PMID: 33968796]
[http://dx.doi.org/10.1371/journal.pone.0278488] [PMID: 36477491]
[http://dx.doi.org/10.3389/fphar.2016.00463] [PMID: 27965580]
[http://dx.doi.org/10.2147/DDDT.S293876] [PMID: 34007158]
[http://dx.doi.org/10.1248/bpb.b19-01072] [PMID: 33504740]
[http://dx.doi.org/10.2174/0929867326666190308133732] [PMID: 31785606]
[http://dx.doi.org/10.1016/j.brainresbull.2020.08.013] [PMID: 32846199]
[PMID: 16549044]
[http://dx.doi.org/10.3389/fneur.2020.00391] [PMID: 32477253]
[http://dx.doi.org/10.1038/s41598-018-29355-0] [PMID: 30026610]
[http://dx.doi.org/10.1186/s12967-020-02386-w] [PMID: 32505218]
[http://dx.doi.org/10.1016/j.trim.2020.101347] [PMID: 33131698]
[http://dx.doi.org/10.1016/j.neulet.2021.135675] [PMID: 33516800]
[http://dx.doi.org/10.1111/jcmm.13596] [PMID: 29536648]
[http://dx.doi.org/10.1007/s13365-017-0571-7] [PMID: 28913617]
[http://dx.doi.org/10.1177/09636897211052975] [PMID: 34662222]
[http://dx.doi.org/10.1152/ajprenal.90530.2008] [PMID: 19535570]
[http://dx.doi.org/10.1016/j.biomaterials.2013.08.015] [PMID: 24064148]
[http://dx.doi.org/10.1155/2020/7057195] [PMID: 32377536]
[http://dx.doi.org/10.1016/j.actbio.2019.04.052] [PMID: 31029828]
[http://dx.doi.org/10.1016/j.jns.2008.06.031] [PMID: 18678377]
[http://dx.doi.org/10.1016/j.jns.2013.02.011] [PMID: 23518370]
[http://dx.doi.org/10.1016/j.pharmthera.2023.108432] [PMID: 37149155]
[http://dx.doi.org/10.1016/j.pharmthera.2007.08.005] [PMID: 17961662]
[http://dx.doi.org/10.1038/nrd3248] [PMID: 21031003]
[http://dx.doi.org/10.1097/WNF.0b013e3181cbf825] [PMID: 20061941]
[http://dx.doi.org/10.1124/jpet.107.123927] [PMID: 17726159]
[http://dx.doi.org/10.1212/WNL.0b013e3181a8260a] [PMID: 19487649]
[http://dx.doi.org/10.1186/s13041-023-01047-5] [PMID: 37438826]
[http://dx.doi.org/10.1002/jnr.24509] [PMID: 31385341]
[http://dx.doi.org/10.1016/j.neuroscience.2015.10.013] [PMID: 26475743]
[http://dx.doi.org/10.3390/ijms232416093] [PMID: 36555733]
[http://dx.doi.org/10.1016/j.brainresbull.2019.08.014] [PMID: 31442591]
[http://dx.doi.org/10.2353/ajpath.2010.091234] [PMID: 20413685]
[http://dx.doi.org/10.3389/fphar.2022.807639] [PMID: 35250559]
[http://dx.doi.org/10.4103/1673-5374.380901] [PMID: 37721276]
[http://dx.doi.org/10.1111/jvim.15309] [PMID: 30506615]
[http://dx.doi.org/10.1111/bph.12620] [PMID: 24641481]
[http://dx.doi.org/10.2478/acph-2022-0029] [PMID: 36651547]
[http://dx.doi.org/10.3389/fimmu.2020.00178] [PMID: 32194542]
[http://dx.doi.org/10.1016/j.lfs.2020.118077] [PMID: 32810509]
[http://dx.doi.org/10.1158/1078-0432.CCR-12-1050] [PMID: 23166225]
[http://dx.doi.org/10.1016/j.cellsig.2010.05.022] [PMID: 20570726]
[http://dx.doi.org/10.18632/oncotarget.7145] [PMID: 27036015]
[http://dx.doi.org/10.1007/s13311-017-0565-4] [PMID: 28812220]
[http://dx.doi.org/10.1371/journal.pone.0039209] [PMID: 22761740]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-2167] [PMID: 22298596]
[http://dx.doi.org/10.3892/ijmm.2020.4796] [PMID: 33236138]
[http://dx.doi.org/10.2174/1871520621666210401105344] [PMID: 33797381]
[http://dx.doi.org/10.3390/ijms232112741] [PMID: 36361531]
[http://dx.doi.org/10.1155/2021/8861766] [PMID: 33506044]
[http://dx.doi.org/10.1016/j.tice.2020.101380] [PMID: 32746988]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2575] [PMID: 24436473]
[http://dx.doi.org/10.1073/pnas.1317630111] [PMID: 24927563]
[http://dx.doi.org/10.1096/fj.201802264R] [PMID: 30917007]
[http://dx.doi.org/10.18632/oncotarget.3012] [PMID: 25726524]
[http://dx.doi.org/10.1186/1878-5085-5-3] [PMID: 24460909]
[http://dx.doi.org/10.18632/oncotarget.4705] [PMID: 26308070]
[http://dx.doi.org/10.1093/carcin/bgi002] [PMID: 15604094]
[http://dx.doi.org/10.1038/sj.emboj.7601518] [PMID: 17245428]
[http://dx.doi.org/10.1271/bbb.67.467] [PMID: 12723592]
[http://dx.doi.org/10.1182/blood-2007-11-121871] [PMID: 18477771]
[PMID: 11888913]
[http://dx.doi.org/10.1074/jbc.RA118.005865] [PMID: 30420430]
[http://dx.doi.org/10.1038/s41419-019-2080-5] [PMID: 31699964]
[http://dx.doi.org/10.1038/s41598-020-60297-8] [PMID: 32076097]
[http://dx.doi.org/10.3892/or.2019.7140] [PMID: 31059070]
[http://dx.doi.org/10.3390/cancers12113388] [PMID: 33207629]
[http://dx.doi.org/10.1182/blood-2013-04-457671] [PMID: 24009232]
[http://dx.doi.org/10.3390/molecules23112750] [PMID: 30355990]
[http://dx.doi.org/10.1177/1177391X0700100002] [PMID: 19812733]
[http://dx.doi.org/10.1016/j.jpba.2014.05.022] [PMID: 24927402]
[http://dx.doi.org/10.1016/j.exphem.2015.04.008] [PMID: 25937048]
[http://dx.doi.org/10.1038/leu.2014.199] [PMID: 24947019]
[http://dx.doi.org/10.1182/blood-2014-12-619155] [PMID: 25931585]
[http://dx.doi.org/10.1016/j.canlet.2019.10.007] [PMID: 31593801]
[http://dx.doi.org/10.1016/j.neuropharm.2014.05.012] [PMID: 24863045]
[http://dx.doi.org/10.1016/j.neuropharm.2021.108464] [PMID: 33460688]
[http://dx.doi.org/10.1016/j.neuropharm.2016.01.031] [PMID: 26808312]
[http://dx.doi.org/10.1016/j.chemphyslip.2015.10.004] [PMID: 26496151]