A cell-permeable naphthoquinone derivative that acts as an ATP-competitive inhibitior against sphingosine kinase 1 (Ki = 280 nM; IC50 = 2 µM; [sphingosine] = 10 µM & [ATP] = 100 µM) and several protein kinases, including, but not limited to, TNK2, AURKB, Met, Syk, AURKC, Fyn, Flt2, PIM2, MST2, CLK1, Tie1, and Fak (% inhibition by 2 µM CB5468139 = 82, 72, 65, 62, 58, 57, 56, 56, 53, 52, 51, and 51, respectively), while exhibiting much reduced potency against DAG Kinase (37% inhibition at 100 µM) and sphingosine kinase 2 (no inhibition at 100 µM; [sphingosine] = 5 µM & [ATP] = 100 µM). CB5468139 is shown to be more potent than SK1/2 dual inhibitor against kidney adenocarcinoma A498 proliferation (GI50 = 10 and 20 µM, respectively; 48 h) and the two inhibitors are also reported to induce differential modulations of A498 cellular ceramides and S1P levels when applied at their respective GI50.
