芬戈莫德(FTY720)是一種免疫抑制劑,通常用于治療多發(fā)性硬化癥,也有抗癌作用,可以作為HDACi(組蛋白脫乙酰酶抑制劑)[1]。

在體外,在7.5或10μM時(shí),芬戈莫德誘導(dǎo)D283和DAOY培養(yǎng)物中的細(xì)胞活力明顯下降,還導(dǎo)致乙?；疕3的水平明顯增加[1]。在體外,Fingolimod對(duì)雄性激素依賴性和非依賴性前列腺癌細(xì)胞顯示出細(xì)胞毒性抗增殖作用,IC50范圍為3.0±0.3至6.8±1.7 μM[2]。Jurkat T淋巴細(xì)胞接觸Fingolimod后,以時(shí)間和濃度依賴的方式抑制延遲整流K+ 電流(IK(DR))的振幅,IC50值為1.51 μM[3]。Fingolimod降低了Ph(+)和Ph(-)ALL細(xì)胞系和患者樣本的增殖和生存能力,其生存能力的IC50值在5.3至7.9 μM之間[4] 。Fingolimod對(duì)OSCC細(xì)胞系SCC4、SCC25和SCC2095的生存能力有不同程度的抑制,IC50值分別為6.1、6.3和4.5 μM[5]。

體內(nèi)試驗(yàn)表明,E13 C57BL/6野生型小鼠在照射4周后,用1 mg/kg的劑量處理,可明顯提高DG(齒狀回)和SVZ(室下區(qū))中DCX+神經(jīng)元的存活率,同時(shí)增殖細(xì)胞也有輕微增加[6]。在體內(nèi),5xFAD小鼠接受1 mg/kg/day的芬戈莫德治療后,外周血淋巴細(xì)胞計(jì)數(shù)和大腦Aβ 水平均下降,但接受0.03 mg/kg/day的治療后,記憶力得到改善,大腦小膠質(zhì)細(xì)胞和星形膠質(zhì)細(xì)胞的激活減少,海馬的GABA和甘油磷酸膽堿水平恢復(fù),對(duì)循環(huán)淋巴細(xì)胞計(jì)數(shù)沒有影響[7]。在體內(nèi),C57BL/6JOlaHsd小鼠接受0.5 mg/kg芬戈莫德治療后,病變大小(中風(fēng))增加,但同側(cè)腦萎縮減少,對(duì)行為結(jié)果沒有影響[8]。

產(chǎn)品性質(zhì)：

Cas No.：162359-56-0

別名：鹽酸芬戈莫德; FTY720

化學(xué)名：2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol;hydrochloride

Canonical SMILES：CCCCCCCCC1=CC=C(C=C1)CCC(CO)(CO)N.Cl

分子式：C19H34ClNO2

分子量：343.94

溶解度：DMSO : ≥ 100 mg/mL; Water : 50 mg/mL

儲(chǔ)存條件：Store at -20°C

注意事項(xiàng)：

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References:

[1] Perla AS, et al. Fingolimod (Fingolimod) reduces viability and survival and increases histone H3 acetylation in medulloblastoma cells. Pediatr Hematol Oncol. 2020 Mar;37(2):170-175.

[2] Allam RM, et al. Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid metabolism within prostate cancer cells. Toxicol Lett. 2018 Jul;291:77-85.

[3] Chang WT, et al. Actions of Fingolimod (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes. Molecules. 2020 Oct 2;25(19):4525.

[4] Wallington-Beddoe CT, et al. Fingolimod produces caspase-independent cell death of acute lymphoblastic leukemia cells. Autophagy. 2011 Jul;7(7):707-15.

[5] Bai LY, et al. Fingolimod Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism. Sci Rep. 2017 Jul 17;7(1):5600.

[6] Metzdorf J, et al. Fingolimod for Irradiation-Induced Neurodegeneration. Front Neurosci. 2019 Jul 9;13:699.

[7] Carreras I, et al. Dual dose-dependent effects of fingolimod in a mouse model of Alzheimer's disease. Sci Rep. 2019 Jul 29;9(1):10972.

[8] Diaz Diaz AC, et al. Preclinical Evaluation of Fingolimod in Rodent Models of Stroke With Age or Atherosclerosis as Comorbidities. Front Pharmacol. 2022 Jul 13;13:920449.