Biological Activity
Opaganib (ABC294640) is a selective, competitive sphingosine kinase 2 (SK2) inhibitor with Ki of 9.8 μM.
In Vitro
Using recombinant human SK1 and SK2, Opaganib demonstrates dose-dependent inhibition of SK2 with an IC50 of approximately 60 μM without affecting the activity of SK1 at concentrations up to at least 100 μM. In contrast, N,N-dimethylsphingosine (DMS) inhibits both SK1 and SK2 with IC50 values of approximately 60 and 20 μM, respectively. Kinetic analyses of varying concentrations of Opaganib (ABC294640) in the presence of 2.5 to 25 μM sphingosine indicated a Ki of 9.8±1.4 μM for the inhibition of SK2. Opaganib (ABC294640) decreases [3H]S1P formation in a dose-dependent fashion with an IC50 value of 26 μM[1]. IC50 values for Opaganib (ABC294640) are approximately 50 and 60 μM for A-498 and Bxpc-3 cells, respectively; whereas the IC50 values for Opaganib (ABC294640) are approximately 20 and 40 μM for these cells[2].
In Vivo
Opaganib induces a transient minor decrease in the hematocrit of rats. Hematology studies indicate decreases in red blood cell number and hematocrit of approximately 20% in animals given either 100 or 250 mg/kg/day; and a slight increase in neutrophils and decrease in basophils in the treated rats[1]. Mice are gavaged with Opaganib (50 mg/kg), a selective inhibitor of sphingosine kinase-2 (SK2), 1 h before surgery and subjected to 1 h-warm ischemia to ~70% of the liver followed by reperfusion. Opaganib-treatment largely prevented the increase of sphingosine-1-phosphate (S1P) after ischemia-reperfusion (IR) in vivo[2].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
