SLM6031434 is an inhibitor of sphingosine kinase 2 (SPHK2) (Ki = 0.4 μM for the recombinant mouse enzyme).1 It is selective for SPHK2 over SPHK1 (Kis = >20 μM). It decreases sphingosine-1-phosphate and increases sphingosine levels in U937 monocytic leukemia cells in a concentration-dependent manner. SLM6031434 (5 mg/kg) reduces blood S1P levels in Sphk1-/-, but not Sphk2-/-, mice. SLM6031434 also increases blood S1P levels in wild-type mice and rats.
|1. Kharel, Y., Morris, E.A., Congdon, M.D., et al. Sphingosine kinase 2 inhibition and blood sphingosine 1-phosphate levels. J. Pharmacol. Exp. Ther. 355(1), 23-31 (2015).