Description
MP-A08 is an ATP-competitive inhibitor of sphingosine kinases SPHK1 and SPHK2 (K
is = 27 and 6.9 μM, respectively). 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; ) without inducing degradation of SPHK1 in Jurkat cells. It induces a 3.7-, 3.5-, and 5.8-fold increase in C-18 ceramide , C-20 ceramide , 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 (EC
50s = 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.
Definition
ChEBI: MP-A08 is a sulfonamide that consists of two moieties of 4-methyl-N-phenylbenzenesulfonamide connected to each other at position 2 by an aldimine linker. It is a ATP-competitive inhibitor of sphingosine kinase that targets both SK1 and SK2 (Ki values of 27 muM and 6.9 muM, respectively) and exhibits anti-cancer properties. It has a role as an antineoplastic agent, an apoptosis inducer, an angiogenesis inhibitor and an EC 2.7.1.91 (sphingosine kinase) inhibitor. It is a sulfonamide, a member of toluenes and an aldimine.
