SKI 178

SKI 178 is an inhibitor of sphingosine kinase 1 (SPHK1) and SPHK2.¹ Though previously thought to be selective for SPHK1, cellular thermal shift assay results demonstrate direct target engagement of both SPHK1 and SPHK2 in HEK293 cells overexpressing either SPHK1 or SPHK2. It inhibits SPHK1 by 59.6% when used at a concentration of 10.7 µM and inhibits the production of sphingosine-1-phosphate (S1P; Item No. 62570) in A549 cells.² SKI 178 is cytotoxic to a variety of cancer cell lines including PANC-1, A549, U251, and MCF-7 cells (IC₅₀s = 0.1, 0.3, 0.5, and 1.3 µM, respectively). It prolongs mitosis and induces cell death through the intrinsic apoptotic pathway in a CDK1-dependent manner.³ SKI 178 (20 mg/kg every other day) reduces the number of white blood cells to a normal range and increases survival in an MLL-AF9 acute myeloid leukemia (AML) mouse xenograft model.¹ It also destabilizes and inhibits microtubule polymerization in an SPHK-independent manner.

WARNING This product is not for human or veterinary use.

1. Hengst, J.A., Dick, T.E., Sharma, A., et al. SKI-178: A multitargeted inhibitor of sphingosine kinase and microtubule dynamics demonstrating therapeutic efficacy in acute myeloid leukemia models. Cancer Transl. Med. 3(4), 109-121 (2017).

2. Hengst, J.A., Wang, X., Sk, U.H., et al. Development of a sphingosine kinase 1 specific small-molecule inhibitor. Bioorg. Med. Chem. Lett. 20(24), 7498-7502 (2010).

3. Dick, T.E., Hengst, J.A., Fox, T.E., et al. The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor SKI-178 in human acute myeloid leukemia cell lines. J. Pharmacol. Exp. Ther. 352(3), 494-508 (2015).