Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide SA 5000, Australia.
Curr Mol Med. 2012 Dec;12(10):1207-19. doi: 10.2174/156652412803833599.
FTY720 is a recently approved first line therapy for relapsing forms of multiple sclerosis. In this context, FTY720 is a pro-drug, with its anti-multiple sclerosis, immunosuppressive effects largely elicited following its phosphorylation by sphingosine kinase 2 and subsequent modulation of G protein-coupled sphingosine 1-phosphate (S1P) receptor 1 that induces lymphopenia by altering lymphocyte trafficking. A number of other biological effects of FTY720 have, however, been described, including considerable evidence that this drug also has anti-cancer properties. These other effects of FTY720 are independent of S1P receptors, and appear facilitated by modulation of a range of other recently described protein targets by nonphosphorylated FTY720. Here, we review the direct targets of FTY720 that contribute to its anti-cancer properties. We also discuss other recently described protein effectors that, in combination with S1P receptors, appear to contribute to its immunosuppressive effects.
FTY720 是一种最近批准的多发性硬化症复发形式的一线治疗药物。在这种情况下，FTY720 是一种前药，其抗多发性硬化症、免疫抑制作用主要是在其被鞘氨醇激酶 2 磷酸化后产生的，随后调节 G 蛋白偶联鞘氨醇 1-磷酸 (S1P) 受体 1，通过改变淋巴细胞的迁移来诱导淋巴细胞减少症。然而，FTY720 还具有许多其他生物学作用，包括大量证据表明该药物还具有抗癌特性。FTY720 的这些其他作用与 S1P 受体无关，并且似乎通过非磷酸化 FTY720 对一系列其他最近描述的蛋白质靶标进行调节而得到促进。在这里，我们回顾了直接作用于 FTY720 的靶点，这些靶点有助于其抗癌特性。我们还讨论了其他最近描述的蛋白质效应物，这些效应物与 S1P 受体结合，似乎有助于其免疫抑制作用。
