Sphingosine 1-phosphate (S1P) is an endogenous signaling molecule that regulates many cellular processes, including cell growth, survival, and movement, upon binding to S1P1-5. It is produced from the phosphorylation of sphingosine by two sphingosine kinase isoenzymes (SphK1 and SphK2). Compared to the well characterized SphK1 little is known of SphK2. The production of S1P is up-regulated in hyperproliferative diseases such as cancer. Our lab is working towards synthesizing three different inhibitors: a dual SphK1 and SphK2 inhibitor as well as SphK1- and SphK2-selective inhibitors to elucidate the different roles each kinase plays within the cell and in disease states. Thus far, we have developed potent SphK1-selective inhibitors as well as a potent dual SphK inhibitor. It is necessary to synthesize a SphK2-selective inhibitor to evaluate its affects on cellular processes. Progress toward the development of SphK2-selective inhibitors is described.

Design and synthesis of sphingosine kinase 2 inhibitors

244th National Meeting (2012)

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