College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Korea.
College of Pharmacy, Chosun University, Gwangju, 61452, Korea.
Molecules. 2018 Oct 24;23(11):2750. doi: 10.3390/molecules23112750.
FTY720 inhibits various cancers through PP2A activation. The structure of FTY720 is also used as a basic structure for the design of sphingosine kinase (SK) inhibitors. We have synthesized derivatives using an amide chain in FTY720 with a phenyl backbone, and then compounds were screened by an MTT cell viability assay. The PP2A activity of compound was examined. The phosphorylation levels of AKT and ERK, downstream targets of PP2A, in the presence of compound , were determined. Compound may exhibit anticancer effects through PP2A activation rather than the mechanism by inhibition of SK1 in cancer cells. In the docking study of compound and PP2A, the amide chain of compound showed an interaction with Asn61 that was different from FTY720, which is expected to affect the activity of the compound.
FTY720 通过激活 PP2A 抑制各种癌症。FTY720 的结构也被用作设计鞘氨醇激酶 (SK) 抑制剂的基本结构。我们使用 FTY720 中的酰胺链和苯环骨架合成了衍生物，然后通过 MTT 细胞活力测定法对化合物进行筛选。检测了化合物的 PP2A 活性。在存在化合物的情况下，测定了 AKT 和 ERK 的磷酸化水平，这是 PP2A 的下游靶标。化合物可能通过激活 PP2A 而不是通过抑制癌细胞中的 SK1 发挥抗癌作用。在化合物与 PP2A 的对接研究中，化合物的酰胺链与 Asn61 表现出不同于 FTY720 的相互作用，这有望影响化合物的活性。
