产品描述:
MP-A08 is an ATP-competitive inhibitor of sphingosine kinases SPHK1 and SPHK2 (Kis = 27 and 6.9 μM, respectively).{38144} It is selective for SPHK1/2 over a panel of 140 human protein kinases at concentrations up to 25 μM. MP-A08 (15 μM) reduces generation of cellular sphingosine-1-phosphate (S1P; Item No. 62570) without inducing degradation of SPHK1 in Jurkat cells. It induces a 3.7-, 3.5-, and 5.8-fold increase in C-18 ceramide (Item No. 19556), C-20 ceramide (Item No. 10724), and C20:1-ceramide levels, respectively, and dose-dependently activates the apoptosis-associated p38 and JNK pathways in vitro. MP-A08 reduces proliferation of a variety of human cancer cell lines (EC50s = 8-44.9 μM). MP-A08 also reduces tumor vasculature, as determined by CD31 staining, and volume as well as S1P protein levels in A549 human lung adenocarcinoma xenografts in mice.