MP-A08 is a highly selective ATP competitive sphingosine kinase (SK) inhibitor that targets both SphK1 and SphK2 with Kivalues of 6.9 ± 0.8 μM and 27 ± 3 μM, respectively.In vitro:MP-A08 blocks pro-proliferative signalling pathways, induces mitochondrial-associated apoptosis in a SK-dependent manner, and reduces the growth of human lung adenocarcinoma tumours in a mouse xenograft model by both inducing tumour cell apoptosis and inhibiting tumour angiogenesis. MP-A08 inhibit SphK2, cause a decrease in EC barrier integrity in vitro in both cell type.[2]In vivo: MP-A08 suppresses the growth of human lung tumor xenografts in mice.
[1]. Pitman MR et al. A selective ATP-competitive sphingosine kinase inhibitor demonstrates anti-cancer properties. Oncotarget, 2015 Mar 30, 6(9):7065-83. [2]. Dimasi DP et al. Examining the Role of Sphingosine Kinase-2 in the Regulation of Endothelial Cell Barrier Integrity. Microcirculation, 2016 Apr, 23(3):248-65.